Enzalutamide

An androgen-receptor (AR) antagonist with IC50 of 36 nM; reduces the efficiency of AR nuclear translocation, and impairs both DNA binding to androgen response elements and recruitment of coactivators; induces tumor regression in mouse models of castration-resistant human prostate cancer; orally available.Prostate cancer Approved (In Vitro) :Enzalutamide (MDV3100) has greater affinity to AR than ICI 176334 does in a competition assay with 16β-[18F]fluoro-5α-DHT (18-FDHT) in castration-resistant LNCaP/AR cells (AR-overexpressing) . While Enzalutamide shows no agonism in LNCaP/AR prostate cells. Enzalutamide antagonizes induction of prostate-specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2), combination with the synthetic androgen R1881 in parental LNCaP cells. Enzalutamide inhibits the transcriptional activity of a mutant AR protein (W741C, mutation of Trp741 to Cys) .Enzalutamide also prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. (In Vivo) :Enzalutamide (MDV3100) induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at a dose of 10 mg/kg.Enzalutamide shows dose-independent pharmacokinetics at intravenous and oral doses of 0.5-5 mg/kg.