Advances in Proteolysis Targeting Chimeras

In recent years, proteolysis-targeting chimeras (PROTACs) have gained widespread attention as an emerging therapeutic approach. PROTACs are bifunctional molecules composed of a target protein-binding ligand, an E3 ubiquitin ligase ligand, and a linker connecting these ligands. By harnessing the cell’s intrinsic ubiquitin-proteasome system (UPS), they promote the ubiquitination of specific target proteins, leading to their degradation and therapeutic effects. PROTACs show exceptional promise in targeting conventional “undruggable” targets compared to traditional small-molecule inhibitors. This review provides an overview of PROTACs, including their molecular mechanism of action, therapeutic benefits, development history, key design aspects, current research and development challenges, and future trends in next-generation PROTAC technology.