Proteolysis-targeting chimera (PROTAC) is an emerging revolutionary technology that promotes degradation of target proteins by proteolysis. AR-targeting PROTACs marked many milestones in the history of PROTAC development. In this review, the author discusses the development of AR-targeting PROTACs over the last two decades. Also included in this focused review are medicinal chemistry strategies, pharmacokinetic profiles and clinical development. Taking AR targeting PROTACs for case study, this review provides a target specific overview of how PROTAC technology has advanced from a revolutionary concept and achieved proof of concept leading to drug candidates that benefit patients.
Keywords: AR; PROTAC; proteolysis; targeted protein degradation.