Apalutamide (ARN-509)

AR

477, 43

Castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors

ARN-509 is in Phase II clinical trial of patients with Prostate Cancer.

30 mg/kg/day

16 nM, 16 nM, 16 nM, 16 nM, 16 nM, 16 nM

ARN-509 (10 mg/kg/d, oral) inhibits tumor growth with decreased proliferative index and increased apoptotic rate in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dose dependently inhibits tumor growth with highest efficacy at dose of 30 mg/kg/day in castrate male immunodeficient mice harboring LNCaP/AR-luc xenograft tumors. ARN-509 dosed at 10 mg/kg/d for 28 days results in a 3-fold reduction in prostates weight associated with lacking glandular secretory activity and 1.7-fold reduction in epididymis weight in adult male dogs. ARN-509 (10 mg/kg/d, oral) inhibits cell proliferation of prostate tissues in adult male dogs. [1] ARN-509 is safe and well tolerated in 24 patients with metastatic CRPC who has progressed on prior treatments and peak plasma concentrations occurred 2 to 3 hours after administration. ARN-509 results in durable PSA declines at doses ranging from 30 to 300 mg in patients with metastatic CRPC. [2] ARN-509 shows powerful anti-cancer activity and induces durable remissions long after therapy completion in castrate resistant prostate cancer mouse models. [3]

Cells are incubated for 48 hours, after which ARN-509 is added in a 16 uL volume to the RPMI culture medium. For the antagonist mode assay, the ARN-509 is diluted in culture medium also containing 30 pM R1881. After 7 days' incubation, 16 uL of CellTiter-Glo Luminescent Cell Viability Assay is added and Relative Luminescence Units (RLUs) measured.

Apalutamide (ARN-509) is a selective and competitive androgen receptor inhibitor with IC50 of 16 nM in a cell-free assay, useful for prostate cancer treatment. Phase 3.