Proteolysis targeting chimera

A proteolysis targeting chimera (PROTAC) is a molecule that can remove specific unwanted proteins. Rather than acting as a conventional enzyme inhibitor, a PROTAC works by inducing selective intracellular proteolysis. A heterobifunctional molecule with two active domains and a linker, PROTACs consist of two covalently linked protein-binding molecules: one capable of engaging an E3 ubiquitin ligase, and another that binds to a target protein. Recruitment of the E3 ligase to the target results in ubiquitination and subsequent degradation of the target protein via the proteasome. Because PROTACs need only to bind their targets with high selectivity (rather than inhibit the target protein's enzymatic activity), efforts are underway to retool previously ineffective inhibitor molecules as PROTACs.