PROTACs: A novel strategy for cancer drug discovery and development

The document reviews the development of proteolysis targeting chimeras (PROTACs) as a novel strategy for cancer drug discovery, emphasizing their ability to degrade target proteins via the ubiquitin-proteasome system. PROTACs show promise in overcoming drug resistance and targeting previously undruggable proteins, with examples like ARCC-4, SJF-0628, MS-39, and LC-2 demonstrating efficacy against resistant cancer types. Despite the potential, the development is limited by the availability of E3 ligase ligands, primarily focusing on VHL and CRBN. The review suggests that future advancements may depend on AI-based structure prediction and DNA-encoded library screening to discover new E3 ligase ligands, enhancing PROTAC technology's scope in cancer therapy.