Varilutamide

Varilutamide (ONC1-13B) is an orally active androgen receptor (AR) inhibitor. Varilutamide shows a rat AR IC₅₀ of 7.9 μM, inhibits DHT-stimulated PSA expression and prostate cancer cell proliferation, suppresses tumor growth and PSA expression and weakly induces lower CYP3A activity. Varilutamide can be used for the research of castration-resistant prostate cancer and prostate cancer^[1]. In Vitro:Varilutamide (ONC1-13B) (1 nM-10 μM; 24 h) potently inhibits DHT-induced PSA expression in LNCaP prostate cancer cells^[1].
Varilutamide (1 nM-10 μM; 5 days) inhibits DHT-induced proliferation of LNCaP prostate cancer cells with an IC₅₀ of 30 nM^[1].
Varilutamide (1 nM-100 μM) binds to rat androgen receptor ligand-binding domain with an IC₅₀ of 7.9 μM^[1].
Varilutamide (1 nM-100 μM) acts as a full androgen receptor antagonist, inhibiting ligand-dependent coactivator recruitment with an IC₅₀ of 19.9 μM without inducing coactivator recruitment on its own^[1].
Varilutamide (10 μM; 60 min) inhibits [³H] GABA binding to rat cerebral cortex membrane homogenates by 42%^[1].
Varilutamide (1-10 μM; 48 h) induces CYP3A activity in human cryopreserved hepatocytes at 10 μM but shows no significant induction at 1 μM^[1]. In Vivo:Varilutamide (ONC1-13B) (20-50 mg/kg; p.o.; daily or twice daily for 21 days) dose-dependently inhibits prostate cancer tumor growth, reduces plasma PSA levels, and suppresses tumor cell proliferation in LNCaP-Z2 xenograft mice, with the 20 mg/kg twice daily dose inducing tumor regression in 50% of treated animals^[1].
Varilutamide (30-300 mg/kg; p.o.; once daily for 14 or 60 days) dose-dependently reduces the weight of androgen-dependent reproductive organs and epididymal sperm concentration in male rats^[1].