Chimera induced protein degradation: PROTACs and beyond
Chimera induced protein degradation: PROTACs and beyond
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嵌合体诱导的蛋白质降解：PROTAC 及其他
DOI：
10.1016/j.ejmech.2020.112494
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发表时间：
2020
影响因子：
6.7
通讯作者：
Hu Qingzhong
中科院分区：
文献类型：
--
作者：
Yin Lina;Hu Qingzhong
泛素-蛋白酶体系统、自噬-溶酶体途径和n端规则途径是人体重要的蛋白质质量控制机制。通过嵌合体降解物劫持这些内源性蛋白质降解措施可能是发现小分子药物的革命性策略。作为最先进的嵌合体降解剂，PROTACs已经通过将两种候选药物送入临床试验，展示了其潜力。综述了利用这三种途径的嵌合体降解物的研究进展，重点从药物化学的角度对其化学结构及其对生物效应的影响进行了综述。
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.