Discovery and biological characterization of a novel series of androgen receptor modulators.

British Journal of Pharmacology
C ZhouM-W Wang

Abstract

Selective androgen receptor modulators are of great value in the treatment of prostate cancer. The purpose of this study was to provide a preliminary characterization of a new class of non-steroidal androgen receptor modulators discovered in a high-throughput screening campaign. Competitive receptor binding, luciferase-based reporter methods, cell proliferation and in vivo assays were employed to evaluate an initial set of compounds from chemistry efforts. Forty-nine analogues from the chemistry efforts showed high affinity binding to androgen receptors, agonist and/or antagonist activities in both CV-1 and MDA-MB-453 transfection assays. A proliferation assay in LNCaP cells also exhibited this profile. A representative of these non-steroidal compounds (compound 21) was devoid of activity at other nuclear receptors (oestrogen, progesterone, glucocorticoid and mineralocorticoid receptors) in the CV-1 co-transfection assay. At the same time, in an immature castrated rat model, it behaved as an androgen receptor antagonist against the growth of prostate, seminal vesicles and levator ani induced by exogenous androgen. Separation of compound 21 into its enantiomers showed that nearly all the androgen receptor modulating activity and...Continue Reading

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Citations

May 7, 2010·The Journal of Pharmacology and Experimental Therapeutics·Amanda JonesJames T Dalton
May 3, 2014·Acta Pharmacologica Sinica·Zhi-yun ZhangMing-wei Wang
Nov 10, 2015·Expert Opinion on Therapeutic Targets·Manuel Luque-Ramírez, Héctor Francisco Escobar-Morreale
Jun 11, 2009·Clinical Endocrinology·Eleanor F NeedGrant Buchanan
Aug 6, 2020·International Journal of Molecular Sciences·Mari Ishigami-Yuasa, Hiroyuki Kagechika
Apr 25, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity

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