A selective androgen receptor modulator for hormonal male contraception

The Journal of Pharmacology and Experimental Therapeutics
Jiyun ChenJames T Dalton

Abstract

The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies, including hormonal male contraception. The identification of an orally bioavailable SARM with the ability to mimic the central and peripheral androgenic and anabolic effects of testosterone would represent an important step toward the "male pill". We characterized the in vitro and in vivo pharmacologic activity of (S)-3-(4-chloro-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide (C-6), a novel SARM developed in our laboratories. C-6 was identified as an androgen receptor (AR) agonist with high AR binding affinity (K(i) = 4.9 nM). C-6 showed tissue-selective pharmacologic activity with higher anabolic activity than androgenic activity in male rats. The doses required to maintain the weight of the prostate, seminal vesicles, and levator ani muscle to half the size of the maximum effects (i.e., ED(50)) were 0.78 +/- 0.06, 0.88 +/- 0.1, and 0.17 +/- 0.04 mg/day, respectively. As opposed to other SARMs, gonadotropin levels in C-6-treated groups were significantly lower than control values. C-6 also significantly decreased serum testosterone conc...Continue Reading

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Citations

Jul 15, 2006·Pharmaceutical Research·Wenqing GaoJames T Dalton
Mar 26, 2010·International Journal of Impotence Research·G J Manetti, S C Honig
May 7, 2010·The Journal of Pharmacology and Experimental Therapeutics·Amanda JonesJames T Dalton
Jul 5, 2005·Molecular Interventions·Jiyun ChenJames T Dalton
Dec 1, 2007·Endocrinology·Jiangang ChenBill L Lasley
Apr 26, 2008·Endocrine Reviews·Stephanie T PageWilliam J Bremner
Jul 18, 2012·Future Medicinal Chemistry·Prabodh Sadana
Apr 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Casey E BohlJames T Dalton
Sep 1, 2005·Women's Health·Ra Anderson, Mj Walton
Jun 10, 2009·Expert Opinion on Therapeutic Patents·Xuqing ZhangZhihua Sui
Mar 22, 2006·Expert Opinion on Investigational Drugs·Scott SegalJames T Dalton
Aug 24, 2006·Expert Opinion on Pharmacotherapy·Sas Barmoshe, Alexandre R Zlotta
Dec 13, 2012·Expert Opinion on Drug Discovery·Xuqing Zhang, Zhihua Sui
Aug 10, 2005·Expert Opinion on Pharmacotherapy·Ammar QoubaitaryChristina Wang
Nov 4, 2016·Physiological Reviews·Maria AlmeidaStavros C Manolagas
Dec 7, 2006·Nature Clinical Practice. Urology·Upendram Srinivas-Shankar, Frederick C W Wu
Dec 17, 2008·Nuclear Receptor Signaling·Ramesh NarayananJames T Dalton
Sep 10, 2010·Clinical Pharmacology and Therapeutics·M Y Roth, J K Amory
May 27, 2009·Current Opinion in Obstetrics & Gynecology·Rajesh K Naz, Shon Rowan
Aug 26, 2006·Nature Clinical Practice. Endocrinology & Metabolism·John K AmoryWilliam J Bremner
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jan TauchenSilvie Rimpelová

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