Philosophy

Biology

Materials science

Proteolysis

Serendipity

Biochemistry

Computational biology

Drug discovery

Nanotechnology

Epistemology

Enzyme

Rational design

Chemistry

Protein degradation

Journal of Medicinal Chemistry

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.

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