ODM-201

ODM-201 is a novel androgen receptor (AR) inhibit designed to inhibit the growth of prostate cancer cells through binding to the AR to inhibit the testosterone-induced AR nuclear translocation. It is particularly used in patients with progressive metastatic castration-resistant prostate cancer. It is effective in inhibiting the activity of some mutant ARs emerging during antiandrogen therapies, including the F876L mutation version which is resistant to enzalutamide and ARN-509 (the second-generation antiandrogens).Therefore, it has potential to overcome the resistance issue occurring upon AR-targeted therapies.
ODM-201 is an androgen receptor (AR) antagonist (Ki= 11 nM). It inhibits AR transactivation in U2OS osteosarcoma cells expressing human wild-type and mutant ARs (IC50s = 65, 66, 1,500, and 1,782 nM for wild-type, ARF876L, ARW741L, and ART877A, respectively). ODM-201 prevents androgen-induced AR nuclear translocation in AR-overexpressing HS-HEK293 and LNCaP cells and suppresses androgen-induced proliferation of VCaP cells (IC50= 230 nM).In vivo, ODM-201 (50 mg/kg per day) reduces tumor growth in a VCaP castrated mouse xenograft model. It also inhibits tumor growth without increasing serum testosterone levels in a VCaP intact mouse xenograft model.