ARD-1676 (ARD1676) is a highly potent and orally efficacious PROTAC degrader of the androgen receptor (AR) with DC50 values of 0.1 and 1.1 nM in AR+ VCaP and LNCaP cell lines, respectively.
ARD-1676 effectively induces degradation of a broad panel of clinically relevant AR mutants with DC50 of 8 nM and Dmax > 95% in the MDA-Pca-2b cell line with AR double mutations (L702H and T878A), but not ARV-110 (Cat# PC-38047).
ARD-1676 exhibits cell growth inhibition in the VCaP and LNCaP cell line cell line with IC50 of 11.5 nM and 18.5 nM, respectively.
ARD-1676 effectively degrades >50% of the AR after a 1 h treatment time and achieved maximum degradation with a 3-6 h treatment time in both the VCaP and LNCaP cell lines at 10 and 100 nM.
ARD-1676 is highly effective and potent in reducing the K388R-, V716M-, W742C-, H875Y-, F877L-, and T878A-mutated AR proteins at concentrations as low as 1 nM, also effectively depletes two AR mutants with Δ388–390 and Δ873–879 deletion, respectively, but much less effective for reducing the levels of AR L702H- and S889G-mutated AR proteins.
ARD-1676 is a selective AR degrader among the >5500 proteins.
ARD-1676 (10-40 mg/kg, oral gavage daily for a total of 21 days) exhibits antitumor activity in the VCaP xenograft tumor model in SCID mice.