molecules of the month

The Michigan bifunctional degrader, ARD-2585, is similar to the Arvinas molecule, ARV-110 that was recently disclosed at AACR 2021. ARV-110 is a first-in-class, potent, and orally active AR degrader in clinical development, but understandably hasn’t had much published on it yet given the competitive environment. The publication of ARD-2585 therefore provides nice insight into the properties of this class of molecules. ARD-2585 interestingly uses a rigid, linear linked piperidine-azetidine linker to connect the AR ligand and CRBN ligand, and is up to 1000x more potent than ARV-110 in AR reduction in vitro, and is active in a xenograft model at 10 mpk QD PO.