Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

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.

Automated summary

Targeted protein degradation through molecular glues is a promising area in drug discovery, offering unique biological activities and physicochemical properties. While classical molecular glue degraders have been serendipitously identified, rational discovery and design strategies are now rapidly emerging.