Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer

doi:10.1016/j.ejmech.2018.01.056

KIZ OpenIR > 科研部门 > 肿瘤生物学（陈策实）

	Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer
	Yuqi Lin 1; Ping Zhao 2; Jinxiang Ye 1; Zheng Zheng 1; Jingan Huang 1; Yingying Zhang 1; Yu Gao 1; Haiying Chen 3; Suling Liu 4,5; Jia Zhou 3; Ceshi Chen 2; Haijun Chen 1
	2018
发表期刊	European Journal of Medicinal Chemistry
期号	146 页码:354-367
摘要	Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers currently with a lack oftargeted therapeutic drugs. Accumulating evidence supports that KLF5 represents a novel therapeutictarget for the treatment of basal TNBC. Our previous studies revealed that mifepristone is capable ofsuppressing TNBC cell proliferation and promoting cancer cell apoptosis by inhibiting KLF5 expression.Nevertheless, its anticancer efficacy is only modest with high dose. Moreover, its main metabolite N-desmethyl mifepristone with the removal of one methyl moiety results in a significant loss of anti-proliferative activity, indicating an important pharmacophore domain around this methyl moiety. Toimprove the pharmacokinetic properties including metabolic stability and enhance the anticancer ac-tivities, a focused compound library by altering this sensitive metabolic region of mifepristone has beendesigned and synthesized for scaffold repurposing and structural optimization. Compound 17 (FZU-00,004) has been identified with an attractive anticancer profile against TNBC via suppressing KLF5expression.
关键词	Triple-negative Breast Cancer Mifepristone Derivatives Sensitive Metabolic Region Klf5 Expression
DOI	10.1016/j.ejmech.2018.01.056
语种	英语
引用统计
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12296
专题	科研部门_肿瘤生物学（陈策实）
通讯作者	Ping Zhao; Ceshi Chen; Haijun Chen
作者单位	1.College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China 2.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, China 3.Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States 4.Key Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China 5.Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
推荐引用方式 GB/T 7714	Yuqi Lin,Ping Zhao,Jinxiang Ye,et al. Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer[J]. European Journal of Medicinal Chemistry,2018(146):354-367.
APA	Yuqi Lin.,Ping Zhao.,Jinxiang Ye.,Zheng Zheng.,Jingan Huang.,...&Haijun Chen.(2018).Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer.European Journal of Medicinal Chemistry(146),354-367.
MLA	Yuqi Lin,et al."Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer".European Journal of Medicinal Chemistry .146(2018):354-367.

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