RD162

RD162, a diarylthiohydantoin, is an orally active non-steroidal antiandrogen (NSAA). RD162 specifically binds to androgen receptor (AR). RD162 induces tumor regression in mouse models of castration-resistant human prostate cancer[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Androgen Receptor

RD162 (1-10 μM; 4 days) suppresses growth and induces apoptosis in the human prostate cancer cell line VCaP which has endogenous AR gene amplification[1]. RD162 has little to no binding to the progesterone, estrogen or glucocorticoid receptors in an in vitro fluorescence polarization assay[1]. Cell Viability Assay[1] Cell Line: VCaP cells Concentration: 1, 10 μM Incubation Time: 4 days Result: Suppressed cell growth.

RD162 (10 mg/kg; oral gavage; daily; for 28 days) causes all tumors regressed[1]. RD162 (0.1, 1, 10 mg/kg; oral gavage; daily; for 5 days) consistently reduces luciferase activity with 10 mg/kg/day human LNCaP/AR xenografts grown in castrated male mice whereas lower doses of 0.1 and 1.0 mg/kg/day has minimal effect. RD162 substantially reduces cellular proliferation after 5 days[1]. RD162 (20 mg/kg; gavage) is ∼50 percent bioavailable after oral delivery with a serum half-life of about 30 hours[1]. Animal Model: Castrate male mice bearing LNCaP/AR xenografts[1] Dosage: 10 mg/kg Administration: Oral gavage; daily; for 28 days Result: Caused all tumors regressed. Animal Model: Male mice[1] Dosage: 20 mg/kg (Pharmacokinetic Analysis) Administration: Oral gavage (in 0.5% hydroxy-methyl-propyl-cellulose) Result: Had ∼50 percent bioavailable after oral delivery with a serum half-life of about 30 hours.

[1]. Chris Tran, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009 May 8;324(5928):787-90.