European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-07-19 , DOI: 10.1016/j.ejmech.2020.112494 Lina Yin 1 , Qingzhong Hu 1
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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.
中文翻译：
嵌合体诱导的蛋白质降解：PROTACs及以后。
泛素-蛋白酶体系统，自噬-溶酶体途径和N端规则途径是人体关键的蛋白质质量控制机制。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，PROTAC通过将两种候选药物用于临床试验证明了其潜力。综述了利用这三种途径的嵌合体降解物的开发，从药物化学的角度着眼于化学结构及其对生物学效应的影响。
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