Chimera induced protein degradation: PROTACs and beyond

被引：12
作者：
Yin, Lina [1 ]
Hu, Qingzhong [1 ]
机构：
[1] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, 232 East Waihuan Rd, Guangzhou 51006, Peoples R China
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 206卷
基金：
中国国家自然科学基金;
关键词：
Chimera degraders; PROTACs; Ubiquitin-proteasome system; Autophagy-lysosome pathway; Drug discovery; N-end rule; PROTEOLYSIS-TARGETING CHIMERAS; E3 UBIQUITIN LIGASE; SMALL MOLECULES; SELECTIVE DEGRADATION; MEDIATED DEGRADATION; ANDROGEN RECEPTOR; DRUG DISCOVERY; BCR-ABL; PROTEASOME; KNOCKDOWN;
D O I：
10.1016/j.ejmech.2020.112494
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Ubiquitin-proteasome system, autophagy-lysosome pathway and N-end rule pathway are crucial protein quality control mechanisms in human body. Hijacking these endogenous protein degrading measures by chimera degraders could be a revolutionary strategy for the discovery of small-molecule drugs. As the most advanced chimera degraders, PROTACs have demonstrated the potential by delivering two drug candidates into clinical trials. The development of chimera degraders exploiting these three pathways are reviewed, a focus is given on the chemical structures and their influences on biological effects from a viewpoint of medicinal chemistry. (C) 2020 Elsevier Masson SAS. All rights reserved.
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页数：17
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