Development of molecular glue: from serendipitous discovery to rational design

Molecular glues can modulate biological functions by specifically inducing interactions between target proteins and E3 ubiquitin ligases, demonstrating significant advantages for disease treatment. However, the discovery of most molecular glues still relies on serendipity, lacking systematic methods and rational design strategies. In recent years, rapid advances in chemical biology and in-depth research on molecular glue-protein interaction mechanisms have gradually enabled systematic development of molecular glues. Therefore, this review aims to organize discovery strategies and representative molecules from three perspectives: serendipitous discovery, screening methods, and rational design, providing critical insights and references for future molecular glue development.