PROTACs: A novel strategy for cancer drug discovery and development

Proteolysis targeting chimera (PROTAC) technology is a promising approach in cancer drug discovery, particularly for targeting undruggable proteins. A PROTAC degrader is composed of a small molecule targeting a protein, an E3 ligase ligand, and a chemical linker. Despite advancements in clinical trials, a significant challenge remains due to the limited availability of E3 ligase recruiters, with only a few available out of over 600 encoded by the human genome. This review highlights the existing RING-type E3 ubiquitin ligases and their small molecule recruiters used as E3 ligands in PROTAC degraders, emphasizing the need for more effective E3 ligase recruiters to enhance targeted protein degradation in anticancer therapies.