tcsc0317 Enzalutamide

Enzalutamide is an androgen-receptor (AR) antagonist with IC₅₀ of 36 nM in LNCaP cells.

IC50 & Target: IC50: 36 nM (androgen-receptor, in LNCaP cells)^[1]

In Vitro: Enzalutamide has greater affinity to AR than Bicalutamide 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)^[1]. Enzalutamide also prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex^[2].

In Vivo: Enzalutamide induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at a dose of 10 mg/kg^[1]. Enzalutamide shows dose-independent pharmacokinetics at intravenous and oral doses of 0.5-5 mg/kg^[4].