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	Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins
	Zhang KY*1; Ding WX1,2,3; Sun J2; Zhang B1; Lu FJ1; Lai R1,4; Zou Y2,5; Yedid G1; Keyunzhang@njau.edu.cn
	2014
发表期刊	BIOCHIMIE
卷号	107期号:Part B页码:203-210
合作性质	其它
摘要	Five 4-arylcoumarins (1c-g) and twelve 3,4-dihydro-4-arylcoumarins (2a-l) were synthesized and tested for antioxidant activity, antitumor activity, toxicity and structure-activity relationships analysis. 4-Arylcoumarins and 3,4-dihydro-4-arylcoumarins that possess two hydroxyl groups in ortho position, such as 1d, 1f, 2a, 2f, 2g and 2h had stronger radical scavenging properties than that of vitamin C (Vit C) in ABTS(center dot+) assay. Kinetic traces of scavenging ABTS(center dot+) and DPPH radicals showed that all the reaction could reached endpoint in 1 min, which was similar with Vit C. 4-Arylcoumarins with 3'-hydroxyl-4'-methylphenyl structural show more efficient NO center dot radical scavenging activity. Three compounds 2e, 1f and 2a, in particular had superior EC50 for NO center dot scavenging than did Vit C. MTT assay indicated that one compound in particular had a potential antitumor effect, inhibiting proliferation of BGC-823 cells and almost completely killing them at a concentration 62.5 mg/L. With same concentration 100 mu g/mL, hemolytic analysis in rabbit red blood cells showed that only two compounds had hemolytic activity with a little more than 5% hemolysis. Injection and oral toxicity tests on Galleria mellonella larvae showed that none of the tested 4-arylcoumarins significantly affected their appetite, viability and mortality. (C) 2014 Elsevier B.V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM).
关键词	Arylcoumarin Antioxidant Radical Scavenging Structure-activity Relationships Antitumor
资助者	This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716).
收录类别	SCI
语种	英语
资助者	This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716). ; This work was supported by Key projects of drug discovery initiative of Ministryof Science and Technologyof People’s Republic of China (2009ZX09103091-002), Science & Technology Program of Guangdong Province (S2013010014278, 2012B091100241) and by National Science Foundation of China (J1210056, 21272280, 81201716).
WOS记录号	WOS:000347742400004
引用统计	被引频次：20[WOS]   [WOS记录]     [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/8266
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
通讯作者	Keyunzhang@njau.edu.cn
作者单位	1.College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China 2.Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, China 3.National Key Laboratory of Pharmaceutical New Technology for Chinese Medicine, Kanion Pharmaceutical Corporation, Lianyungang, China 4.Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223 Yunnan, China 5.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
推荐引用方式 GB/T 7714	Zhang KY*,Ding WX,Sun J,et al. Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins[J]. BIOCHIMIE,2014,107(Part B):203-210.
APA	Zhang KY*.,Ding WX.,Sun J.,Zhang B.,Lu FJ.,...&Keyunzhang@njau.edu.cn.(2014).Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins.BIOCHIMIE,107(Part B),203-210.
MLA	Zhang KY*,et al."Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins".BIOCHIMIE 107.Part B(2014):203-210.

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