BMS-564,929
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| Other names | PS-178990 |
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| ECHA InfoCard | 100.233.303 |
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| Formula | C14H12ClN3O3 |
| Molar mass | 305.72g·mol−1 |
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BMS-564,929is an investigationalselective androgen receptor modulator(SARM) which is being developed byBristol-Myers Squibbfor treatment of the symptoms of age-related decline in androgen levels in men ( "andropause"). These symptoms may includedepression,loss ofmusclemass andstrength,reduction inlibidoandosteoporosis.Treatment with exogenoustestosteroneis effective in counteracting these symptoms but is associated with a range of side effects, the most serious of which is enlargement of theprostate gland,which can lead tobenign prostatic hypertrophyand evenprostate cancer.This means there is a clinical need for selective androgen receptor modulators, which produceanaboliceffects in some tissues such as muscle and bone, but without stimulating androgen receptors in the prostate.[1]
BMS-564,929 is one such compound currently in early human clinical trials, which is an orally active, potent and selective agonist for androgen receptors (Ki2.1nM, 20xfunctional selectivityfor muscle tissue over prostate) and in studies on castrated rats it was shown to counteract decrease in muscle mass over time, and at higher doses even increased muscle mass, without significantly affecting prostate tissue.[2]It does however vastly reduceluteinizing hormonelevels, it being an astonishing 33× more suppressive compound than testosterone, which may be a problem in human clinical use.[3]
Selective androgen receptor modulators may also be used by athletes to assist in training and increase physical stamina and fitness, potentially producing effects similar toanabolic steroidsbut with significantly fewer side effects. For this reason, SARMs have already been banned by theWorld Anti-Doping Agencysince January 2008 despite no drugs from this class yet being in clinical use, and blood tests for all known SARMs are currently being developed.[4][5]
References
[edit]- ^Gao W, Dalton JT (March 2007)."Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)".Drug Discovery Today.12(5–6): 241–8.doi:10.1016/j.drudis.2007.01.003.PMC2072879.PMID17331889.
- ^Ostrowski J, Kuhns JE, Lupisella JA, Manfredi MC, Beehler BC, Krystek SR, et al. (January 2007)."Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats".Endocrinology.148(1): 4–12.doi:10.1210/en.2006-0843.PMID17008401.
- ^Gao W, Dalton JT (February 2007)."Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5 Alpha -reductase?".Molecular Interventions.7(1): 10–3.doi:10.1124/mi.7.1.3.PMC2040232.PMID17339601.
- ^Thevis M, Kohler M, Schlörer N, Kamber M, Kühn A, Linscheid MW, Schänzer W (May 2008). "Mass spectrometry of hydantoin-derived selective androgen receptor modulators".Journal of Mass Spectrometry.43(5): 639–50.Bibcode:2008JMSp...43..639T.doi:10.1002/jms.1364.PMID18095383.
- ^Thevis M, Kohler M, Thomas A, Maurer J, Schlörer N, Kamber M, Schänzer W (May 2008). "Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC-MS/MS".Analytical and Bioanalytical Chemistry.391(1): 251–61.doi:10.1007/s00216-008-1882-6.PMID18270691.S2CID206899531.