ARD-2128 is a highly potent, orally bioavailable PROTAC (proteolysis-targeting chimera) that degrades the androgen receptor (AR), effectively reducing AR protein levels, suppressing AR-regulated gene expression in tumor tissues, and inhibiting tumor growth without evident toxicity. This compound holds promise for prostate cancer research.

VCaP:4 nM (IC50), LNCaP cells:5 μM (IC50)

ARD-2128 exhibits high potency and efficacy in suppressing the growth of both VCaP and LNCaP cell lines, with IC50 values of 4 nM and 5 nM, respectively [1]. Notably, in the VCaP cell line treated with ARD-2128 at concentrations of 1, 10, 100, and 1000 nM for 24 hours, there is a significant decrease in AR protein levels, with reductions of more than 50% observed at 1 nM and over 90% degradation at concentrations of 10, 100, and 1000 nM [1]. This finding is further corroborated by a Cell Viability Assay [1], which demonstrates that ARD-2128 effectively diminishes AR protein levels and facilitates AR degradation in the VCaP cell line under the specified conditions.

ARD-2128 administered orally at a dosage of 20 mg/kg effectively lowers AR protein levels in mice within 24 hours, as per reference [1]. When given daily at doses ranging from 10 to 40 mg/kg for 21 days, the compound demonstrates notable antitumor effects in the VCaP xenograft mouse model, inhibiting tumor growth by 46% to 69% [1]. Pharmacokinetic analysis reveals that a 5 mg/kg oral dosage yields a maximum concentration (C max) of 1304 ng/mL, an area under the curve (AUC 0-t) of 22361 ng h/mL, and a half-life (t 1/2) of 18.8 hours [1]. The study, using SCID and Male ICR mice, indicates that ARD-2128, with oral bioavailability of 67%, effectively reduces AR protein levels and suppresses AR-regulated gene activity in tumor tissues. It thus inhibits tumor growth in mice without observable toxicity.