The Role of New Technologies and Strategies in Drug Discovery for Undruggable Targets

Drug target discovery, a critical part of modern drug development, is essential for achieving high selectivity and therapeutic efficacy. As an emerging technology that combines proteomics with chemical biology, chemical proteomics has advanced target discovery. This review presents breakthrough technologies and strategies for targeting traditionally undruggable proteins, including protein degraders and covalent inhibitors, and explores the role of chemical proteomics-based target identification technologies in the discovery of therapeutics for these undruggable targets, aiming to provide new insights and directions for overcoming the limitations of undruggable targets.