ARD-1676 is an orally available androgen receptor (AR) PROTAC degrader, consisting of AR ligand and cereblon ligand. ARD-1676 has AR-degrading activity in vitro and in vivo and inhibits VCaP tumor growth in mouse xenograft tumor models.
The DC50 values of ARD-1676 for AR degradation in AR+ VCaP and LNCaP cell lines are 0.1 and 1.1 nM, respectively, and the IC50 values in VCaP and LNCaP cell lines are 11.5 and 2.8 nM respectively[1].
The oral bioavailability of ARD-1676 was 67%, 44%, 31%, and 99% in mice, rats, dogs, and monkeys, respectively. ARD-1676 effectively reduces AR protein levels in mouse VCaP tumor tissues and inhibits tumor growth in VCaP mouse xenograft tumor models[1].
References:
[1]. Xiang W, et al. Discovery of ARD-1676 as a Highly Potent and Orally Efficacious AR PROTAC Degrader with a Broad Activity against AR Mutants for the Treatment of AR + Human Prostate Cancer. J Med Chem. 2023 Sep 8..