Structure鈥揂ctivity Relationships in Non-Ligand Binding Pocket (Non-LBP) Diarylhydrazide Antiandrogens

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• 作者：Laura Caboni ; Billy Egan ; Brendan Kelly ; Fernando Blanco ; Darren Fayne ; Mary J. Meegan ; David G. Lloyd
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2013
• 出版时间：August 26, 2013
• 年：2013
• 卷：53
• 期：8
• 页码：2116-2130
• 全文大小：825K
• 年卷期：v.53,no.8(August 26, 2013)
• ISSN：1549-960X

文摘

We report the synthesis and a study of the structure鈥揳ctivity relationships of a new series of diarylhydrazides as potential selective non-ligand binding pocket androgen receptor antagonists. Their biological activity as antiandrogens in the context of the development of treatments for castration resistant prostate cancer was evaluated using in vitro time resolved fluorescence resonance energy transfer and fluorescence polarization on target assays. Additionally, a theoretical study combining docking and molecular dynamics methods was performed to provide insight into their mechanism of action as a basis for further lead optimization studies.