Apalutamide

Apalutamide (ARN-509) is a potent and competitive androgen receptor (AR) antagonist, binding AR with an IC₅₀ of 16 nM^[1]. IC50 & Target: IC50: 16 nM (Androgen receptor)^[1] In Vitro: Apalutamide (ARN-509) also exhibits low micromolar affinity (IC₅₀ 3 μM) for the GABA_A receptor in radioligand binding-assays and thus may potentially antagonize GABA_A at therapeutic dose levels^[1]. Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets^[2]. In Vivo: Apalutamide (ARN-509) exhibits low systemic clearance, high oral bioavailability and long plasma half-life in both mouse and dog, supporting once-daily oral dosing. Consistent with its long terminal-half-life, Apalutamide steady-state plasma-levels increases in repeat-dose studies, resulting in high C_24hr levels and low peak:trough ratios (ratio:2.5). Castrate male mice bearing LNCaP/AR xenograft tumors are treated with either Apalutamide at doses of 1, 10 or 30 mg/kg/day. Thirteen of 20 Apalutamide (30 mg/kg/day)-treated animals exhibit >50% reduction in tumor-volume at day 28 versus 3 of 19 MDV3100 (30 mg/kg/day)-treated mice^[1].