ARCC-4 is a potent, selective enzalutamide-based von Hippel-Lindau (VHL)-recruiting androgen receptor (AR) degrader with DC50 of 5 nM in VCaP cells. ARCC-4 is better at overcoming resistance in cellular models of castration-resistant prostate cancer (CRPC). ARCC-4 is better than enzalutamide at inducing apoptosis and inhibiting proliferation of AR-amplified prostate cancer cells. ARCC-4 effectively degrades clinically relevant AR mutants associated with antiandrogen therapy, and maintains its potency to degrade AR and inhibit cell proliferation in a high androgen environment in which enzalutamide has no activity.
