A ligand-based approach to identify quantitative structure-activity relationships for the androgen receptor

Journal of Medicinal Chemistry
Casey E BohlJ T Dalton

Abstract

We examined the three-dimensional quantitative structure-activity relationship (QSAR) of a group of endogenous and synthetic compounds for the androgen receptor (AR) using comparative molecular field analysis (CoMFA). The goal of these studies was to identify structural features necessary for high binding affinity and optimization of selective androgen receptor modulators (SARMs). A homology model of the AR was used as a scaffold to align six lead compounds that served as templates for alignment of the remaining 116 structures prior to CoMFA modeling. The conventional r(2) and cross-validated q(2) relating observed and predicted relative binding affinity (RBA) were 0.949 and 0.593, respectively. Comparison of predicted and observed RBA for a test set of 10 compounds resulted in an r(2) of 0.954, demonstrating the excellent predictive ability of the model. These integrated homology modeling and CoMFA studies identified critical amino acids for SARM interactions and provided QSAR data as the basis for mechanistic studies of AR structure, function, and design of optimized SARMs.

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Feb 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·Donghua YinJames T Dalton

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Citations

Jul 15, 2006·Pharmaceutical Research·Wenqing GaoJames T Dalton
Apr 21, 2005·Analytical Biochemistry·Helena NordinOlof P Karlsson
Dec 15, 2007·Tetrahedron Letters·Vipin A NairDuane D Miller
Sep 15, 2005·Chemical Reviews·Wenqing GaoJames T Dalton
Sep 21, 2013·Environmental Science & Technology·Xiaoxiang WangHongxia Yu
Sep 1, 2005·The Journal of Biological Chemistry·Casey E BohlJames T Dalton
Mar 4, 2008·SAR and QSAR in Environmental Research·A PanayeJ M Porcher
Jan 26, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jun YangJames T Dalton
May 7, 2010·The Journal of Pharmacology and Experimental Therapeutics·Amanda JonesJames T Dalton
Jul 5, 2005·Molecular Interventions·Jiyun ChenJames T Dalton
Apr 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Casey E BohlJames T Dalton
Jan 1, 2010·Expert Opinion on Drug Discovery·Tommi H Nyrönen, Annu A Söderholm
Dec 25, 2012·Ecotoxicology and Environmental Safety·Xiaoxiang WangYulei Wang
May 8, 2007·Toxicology and Applied Pharmacology·Jiangang ChenBill L Lasley
Apr 18, 2009·Journal of Mass Spectrometry : JMS·Mario ThevisWilhelm Schänzer
Nov 14, 2006·Advanced Drug Delivery Reviews·Cheng ChangPeter W Swaan
Nov 9, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Cheng Chang, Peter W Swaan
Aug 10, 2005·Expert Opinion on Pharmacotherapy·Ammar QoubaitaryChristina Wang
May 17, 2005·Drug Discovery Today·Cheng ChangPeter Swaan
Dec 17, 2008·Nuclear Receptor Signaling·Ramesh NarayananJames T Dalton
Jan 12, 2019·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Sugunadevi SakkiahHuixiao Hong
Mar 11, 2005·Expert Review of Anticancer Therapy·Scott M Dehm, Donald J Tindall
Jun 27, 2008·Molecular Pharmacology·Sean EkinsSridhar Mani
Jul 11, 2006·Bioorganic & Medicinal Chemistry·Dong Jin HwangDuane D Miller
Apr 10, 2018·Journal of the American Chemical Society·Qian ShaoJin-Quan Yu
Nov 20, 2020·Environmental Science & Technology·Kimberley M ZornSean Ekins
Oct 13, 2017·Journal of Chemical Information and Modeling·Daniela TrisciuzziOrazio Nicolotti
Oct 22, 2020·Environmental Science & Technology·Kimberley M ZornSean Ekins

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