PROTAC as a Potential Toolbox for the Discovery of New Targets and Drugs.

With its event-driven degradation mechanism, proteolysis targeting chimera (PROTAC) is emerging as a powerful toolbox for novel drug discovery and target identification. In drug discovery, PROTAC enables the targeting of traditionally undruggable proteins, disrupts protein scaffolding functions, overcomes clinical drug resistance, and enhances target selectivity. In target identification, derivatizing bioactive molecules into PROTAC probes combined with proteomics permits precise identification of drug targets; furthermore, target-agnostic PROTAC libraries and tag-based degradation systems facilitate the de novo discovery and functional validation of unknown targets. PROTAC technology has evolved from a mere intervention tool to an integrated platform for new target and drug discovery, providing transformative strategies for precision medicine and innovative drug development.