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• W2068152079 abstract "BACKGROUND Molecular basis for secondary antiandrogen therapy in prostate cancer with mutant androgen receptors (ARs) is not fully elucidated. MATERIALS AND METHODS Effects of steroidal and non-steroidal antiandrogens on transcriptional activities of wild-type and mutant (W741C, T877A, and W741C+T877A) ARs were measured. Crystal structure analysis and docking studies were performed using Molecular Operating Environment (MOE) package. RESULTS DHT-induced transcriptional activity of the T877A mutant and the W741C mutant was suppressed by bicalutamide and hydroxyflutamide, respectively. Nilutamide suppressed the W741C mutant and the double mutant. Cyproterone acetate modestly inhibited the W741C mutant and the double mutant. The structural studies suggested that nilutamide and cyproterone acetate retain their antiandrogenic properties against both the W741C mutant and the double mutant due to fact that mutation W741C does not permit formation of key hydrophobic interaction between ligand and AR ligand binding domain, which is necessary for their conversion into agonists. CONCLUSIONS Switching antiandrogens may be reasonable in prostate cancer with mutant ARs. Prostate 67: 799–807, 2007. © 2007 Wiley-Liss, Inc." @default.
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• W2068152079 date "2007-01-01" @default.
• W2068152079 modified "2023-10-11" @default.
• W2068152079 title "Effects of steroidal and non-steroidal antiandrogens on wild-type and mutant androgen receptors" @default.
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• W2068152079 doi "https://doi.org/10.1002/pros.20542" @default.
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