Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions.In recent years,molecular glues have been widely used as protein degraders.In addition,however,molecula...Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions.In recent years,molecular glues have been widely used as protein degraders.In addition,however,molecular glues play a variety of vital roles,such as complex stabilization,interactome modulation and transporter inhibition,enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery.Since most molecular glues are identified serendipitously,exploration of their systematic discovery and rational design are important.In this review,representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization,homo-polymerization and hetero-dimerization according to their aggregation modes,and we attempt to elucidate their mechanisms of action.In particular,we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development:starting point,optimization and identification.展开更多
基金supported from the National Natural Science Foundation of China (Nos. 82173672, 82173679, 81903446 and 81973167, China)Natural Science Foundation of Jiangsu Province (BK20190564, China)+1 种基金“Double First-Class” University project of China Pharmaceutical University (CPU2018GY04, China)Free exploration basic research project of Shenzhen Virtual University Park (2021Szvup162, China) for financial support
文摘Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions.In recent years,molecular glues have been widely used as protein degraders.In addition,however,molecular glues play a variety of vital roles,such as complex stabilization,interactome modulation and transporter inhibition,enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery.Since most molecular glues are identified serendipitously,exploration of their systematic discovery and rational design are important.In this review,representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization,homo-polymerization and hetero-dimerization according to their aggregation modes,and we attempt to elucidate their mechanisms of action.In particular,we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development:starting point,optimization and identification.
