Rational discovery of molecular glue degraders based on block chemistry

Abstract

Molecular glue degraders (MGDs) have emerged as promising therapeutic agents with substantial clinical potential and growing commercial interest in terms of their pharmaceutical development. Nevertheless, the translation of MGDs into clinical trials remains limited. Recent advances in drug discovery technologies are facilitating a paradigm shift in MGD development, from serendipitous discovery to rational design. Here, we systematically analyze rational MGD discovery strategies, focusing on E3 ligase and target ligand modifications. Furthermore, we highlight cutting-edge technologies and the latest trends in MGD development. Thus, this review provide valuable insights for researchers and could help accelerate the clinical translation of MGDs.