Proteolysis targeting chimera

A proteolysis targeting chimera (PROTAC) is a two-headed molecule capable of removing unwanted proteins by inducing selective intracellular proteolysis. PROTACs consist of two linked protein binding molecules, one capable of engaging an E3 ubiquitin ligase and the other to a target protein meant for degradation by the cellular protein quality control machinery. Recruitment of the target protein to the specific E3 ligase results in its tagging for destruction (i.e., ubiquitination) and subsequent degradation by the proteasome. Initially described by Craig Crews and Ray Deshaies in 2001, the PROTAC technology has been applied by a number of drug discovery labs to various E3 ligases, including pVHL, MDM2, beta-TrCP1, cereblon, and c-IAP1. Yale University licensed the PROTAC technology to Arvinas in 2013-14.