Liver-targeting chimeras as a potential modality for the treatment of liver diseases

	Liver-targeting chimeras as a potential modality for the treatment of liver diseases
	Chen, CJ; Pan, YZ; Yang, XY; Li, HQ; Cai, XH; He, SY; Wang, Q; Yang, YW; Zheng, RZ; Li, HW; Yuan, SJ; Dong, X; Samarawickrama, PN; Zi, MT; He, YH; Zhang, X
	2024
发表期刊	JOURNAL OF CONTROLLED RELEASE
ISSN	0168-3659
卷号	374 页码:627-638
摘要	Liver diseases pose significant challenges to global public health. In the realm of drug discovery and development, overcoming 'on-target off-tissue' effects remains a substantial barrier for various diseases. In this study, we have pioneered a Liver-Targeting Chimera (LIVTAC) approach using a proteolysis-targeting chimera (PROTAC) molecule coupled to the liver-specific asialoglycoprotein receptor (ASGPR) through an innovative linker attachment strategy for the precise induction of target protein degradation within the liver. As a proof-of-concept study, we designed XZ1606, a mammalian bromodomain and extra-terminal domain (BET)-targeting LIVTAC agent, which not only demonstrated enduring tumor suppression (over 2 months) in combination with sorafenib but also an improved safety profile, notably ameliorating the incidence of thrombocytopenia, a common and severe on-target dose-limiting toxic effect associated with conventional BET inhibitors. These encouraging results highlight the potential of LIVTAC as a versatile platform for addressing a broad spectrum of liver diseases.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14469
专题	科研部门_衰老调控与功能研究（何永捍）
推荐引用方式 GB/T 7714	Chen, CJ,Pan, YZ,Yang, XY,et al. Liver-targeting chimeras as a potential modality for the treatment of liver diseases[J]. JOURNAL OF CONTROLLED RELEASE,2024,374:627-638.
APA	Chen, CJ.,Pan, YZ.,Yang, XY.,Li, HQ.,Cai, XH.,...&Zhang, X.(2024).Liver-targeting chimeras as a potential modality for the treatment of liver diseases.JOURNAL OF CONTROLLED RELEASE,374,627-638.
MLA	Chen, CJ,et al."Liver-targeting chimeras as a potential modality for the treatment of liver diseases".JOURNAL OF CONTROLLED RELEASE 374(2024):627-638.

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