Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery
Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery
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DOI：
10.1021/acs.jmedchem.1c00895
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发表时间：
2021-07-28
影响因子：
7.3
通讯作者：
Sheng, Chunquan
中科院分区：
文献类型：
--
作者：
Dong, Guoqiang;Ding, Yu;Sheng, Chunquan
靶向蛋白质降解是发现和发展创新疗法的一个很有前途的领域。分子胶介导了邻近诱导的蛋白质降解，与异双功能蛋白水解靶向嵌合体相比具有固有的优势，包括前所未有的机制、独特的生物活性和良好的物理化学性质。经典的分子胶降解剂已经被偶然发现，但理性的发现和设计策略正在迅速出现。在这篇综述中，我们旨在重点介绍用于靶向蛋白质降解的分子胶的最新进展，并讨论将分子胶开发成治疗剂的挑战。特别是，将讨论发现战略、行动机制和有代表性的案例研究。
Targeted protein degradation is a promising area in the discovery and development of innovative therapeutics. Molecular glues mediate proximity-induced protein degradation and have intrinsic advantages over heterobifunctional proteolysis-targeting chimeras, including unprecedented mechanisms, distinct biological activities, and favorable physicochemical properties. Classical molecular glue degraders have been identified serendipitously, but rational discovery and design strategies are emerging rapidly. In this review, we aim to highlight the recent advances in molecular glues for targeted protein degradation and discuss the challenges in developing molecular glues into therapeutic agents. In particular, discovery strategies, action mechanisms, and representative case studies will be addressed.