Enobosarm: Difference between revisions
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In June 2013, professional cyclist [[Nikita Novikov]] was provisionally suspended after a possible breach of anti-doping rules, due to a positive A-sample result for Ostarine. <ref>http://www.vacansoleildcm.co.uk/nieuws/nikita-novikov-provisionally-suspended-after-possible-breach-of-anti-doping-rules.html</ref> |
In June 2013, professional cyclist [[Nikita Novikov]] was provisionally suspended after a possible breach of anti-doping rules, due to a positive A-sample result for Ostarine. <ref>http://www.vacansoleildcm.co.uk/nieuws/nikita-novikov-provisionally-suspended-after-possible-breach-of-anti-doping-rules.html</ref> |
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==Clinical trials== |
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In December 2006, GTx completed a 3 month Phase II double-blind, randomized, placebo-controlled [[clinical trial]] in 120 subjects (60 elderly men and 60 postmenopausal women). Enobosarm treatment resulted in a dose-dependent increase in [[body composition|lean body mass]] (LBM), with those taking the highest dose of 3mg per day showing an average LBM increase of 1.4 kg (3.1 lbs) compared to those who received [[placebo]]. The Enobosarm treatment also resulted in improvement in muscle function (performance) in a 12 stair climb test measuring speed and power. Enobosarm had a favorable safety profile, with no serious adverse events reported. Enobosarm also exhibited tissue selectivity with beneficial effects on lean body mass and performance and with no apparent change in measurements of [[Prostate-specific antigen|serum PSA]], [[sebum]] production or serum [[Luteinizing hormone|LH]].<ref name="GTxWebsite">http://www.gtxinc.com/Pipeline/OstarineMK2866.aspx?Sid=4</ref> |
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In October 2008, GTx announced topline results of the Phase II trial evaluating Enobosarm in patients with cancer [[cachexia]]. The clinical trial enrolled 159 cancer patients (average age of 66 years) with non-small cell lung cancer, colorectal cancer, non-Hodgkin lymphoma, chronic lymphocytic leukemia or breast cancer at 35 sites in the U.S. and Argentina. Participants were randomized to receive placebo, 1mg or 3mg oral capsule of Enobosarm once daily for 16 weeks. Average reported weight loss prior to entry among all subjects was 8.8%. Subjects were allowed to have standard chemotherapy during the trial. The study met its primary endpoint of absolute change in total lean body mass (muscle) compared to placebo and the secondary endpoint of muscle function (performance). The incidence of serious adverse events, deaths and tumor progression were similar among placebo and the treatment arms. The most common side effects reported among all subjects in the trial were fatigue, anemia, nausea and diarrhea.<ref name="GTxWebsite" /> |
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GTx and Merck had clinical development plans to evaluate Enobosarm for the treatment of muscle loss in patients with [[COPD]] and for the treatment of chronic [[sarcopenia]]. They had a goal of initiating an Enobosarm Phase II COPD clinical trial in the first quarter of 2010 and an Enobosarm Phase IIb chronic sarcopenia clinical trial in 2010.<ref>http://www.faqs.org/sec-filings/091109/GTX-INC-DE-_10-Q/</ref> |
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http://upload.wikimedia.org/wikipedia/commons/5/51/2010-04-23_Ostarine_vs_Andarine.TIF |
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== References == |
== References == |
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Revision as of 02:11, 15 January 2015
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| Clinical data | |
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| Routes of administration | Oral |
| ATC code |
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| Legal status | |
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| Pharmacokinetic data | |
| Elimination half-life | 24 hours [citation needed] |
| Identifiers | |
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| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C19H14F3N3O3 |
| Molar mass | 389.33 g/mol g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 70 to 74 °C (158 to 165 °F) |
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Enobosarm ((2S)-3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide) (also known as Ostarine, GTx-024 and MK-2866) is an investigational selective androgen receptor modulator (SARM) from GTX, Inc for treatment of conditions such as muscle wasting and osteoporosis, formerly under development by Merck & Company.[1]
Structure
According to a recent paper authored by GTx, "Readers are cautioned to note that the name Ostarine is often mistakenly linked to the chemical structure of [S-4], which is also known as andarine. The chemical structure of Ostarine has not been publicly disclosed."[2] While GTx has not formally disclosed the structure of Ostarine, the chemical composition of Ostarine is revealed in patent databases such the WIPO[3] and discussed by Zhang et al., 2009 in the primary literature.[4] Various SARM chemotypes exist (aryl propionamides, quinolines, quinolinones, bicyclic hydantoins), though aryl propionamides such as Ostarine, Andarine/S-4, and S-23 represent some of the most advanced putative therapeutics under investigation.[5] In terms of atom connectivity, Enobosarm differs from Andarine by cyano substitutions on the phenyl rings as it replaces both the nitro and acetamido moieties.
Doping
Selective androgen receptor modulators may be used by athletes to assist in training and increase physical stamina and fitness, potentially producing effects similar to anabolic steroids. For this reason, SARMs were banned by the World Anti-Doping Agency in January 2008 despite no drugs from this class yet being in clinical use, and blood tests for all known SARMs have been developed.[6][7]
In June 2013, professional cyclist Nikita Novikov was provisionally suspended after a possible breach of anti-doping rules, due to a positive A-sample result for Ostarine. [8]
Clinical trials
In December 2006, GTx completed a 3 month Phase II double-blind, randomized, placebo-controlled clinical trial in 120 subjects (60 elderly men and 60 postmenopausal women). Enobosarm treatment resulted in a dose-dependent increase in lean body mass (LBM), with those taking the highest dose of 3mg per day showing an average LBM increase of 1.4 kg (3.1 lbs) compared to those who received placebo. The Enobosarm treatment also resulted in improvement in muscle function (performance) in a 12 stair climb test measuring speed and power. Enobosarm had a favorable safety profile, with no serious adverse events reported. Enobosarm also exhibited tissue selectivity with beneficial effects on lean body mass and performance and with no apparent change in measurements of serum PSA, sebum production or serum LH.[9]
In October 2008, GTx announced topline results of the Phase II trial evaluating Enobosarm in patients with cancer cachexia. The clinical trial enrolled 159 cancer patients (average age of 66 years) with non-small cell lung cancer, colorectal cancer, non-Hodgkin lymphoma, chronic lymphocytic leukemia or breast cancer at 35 sites in the U.S. and Argentina. Participants were randomized to receive placebo, 1mg or 3mg oral capsule of Enobosarm once daily for 16 weeks. Average reported weight loss prior to entry among all subjects was 8.8%. Subjects were allowed to have standard chemotherapy during the trial. The study met its primary endpoint of absolute change in total lean body mass (muscle) compared to placebo and the secondary endpoint of muscle function (performance). The incidence of serious adverse events, deaths and tumor progression were similar among placebo and the treatment arms. The most common side effects reported among all subjects in the trial were fatigue, anemia, nausea and diarrhea.[9]
GTx and Merck had clinical development plans to evaluate Enobosarm for the treatment of muscle loss in patients with COPD and for the treatment of chronic sarcopenia. They had a goal of initiating an Enobosarm Phase II COPD clinical trial in the first quarter of 2010 and an Enobosarm Phase IIb chronic sarcopenia clinical trial in 2010.[10]
http://upload.wikimedia.org/wikipedia/commons/5/51/2010-04-23_Ostarine_vs_Andarine.TIF
References
- ^ James T. Dalton, Duane D. Miller, Donghua Yin, Yali He. Selective androgen receptor modulators and methods of use thereof. US Patent 6569896
- ^ Mohler ML, Bohl CE, Jones A; et al. (June 2009). "Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit". J. Med. Chem. 52 (12): 3597–617. doi:10.1021/jm900280m. PMID 19432422.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ WO application 2008127717, James T. Dalton and Duane D. Miller, "Selective Androgen Receptor Modulators for Treating Diabetes", published Oct 23, 2008, assigned to University of Tennessee Research Foundation, James T. Dalton, and Duane D. Miller
- ^ Zhang X, Lanter JC, Sui Z (September 2009). "Recent advances in the development of selective androgen receptor modulators". Expert Opin Ther Pat. 19 (9): 1239–58. doi:10.1517/13543770902994397. PMID 19505196.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Jones A, Chen J, Hwang DJ, Miller DD, Dalton JT (January 2009). "Preclinical characterization of a (S)-N-(4-cyano-3-trifluoromethyl-phenyl)-3-(3-fluoro, 4-chlorophenoxy)-2-hydroxy-2-methyl-propanamide: a selective androgen receptor modulator for hormonal male contraception". Endocrinology. 150 (1): 385–95. doi:10.1210/en.2008-0674. PMC 2630904. PMID 18772237.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Thevis M, Kohler M, Schlörer N, Kamber M, Kühn A, Linscheid MW, Schänzer W. Mass spectrometry of hydantoin-derived selective androgen receptor modulators. Journal of Mass Spectrometry. 2008 May;43(5):639-50. PMID 18095383
- ^ Thevis M, Kohler M, Thomas A, Maurer J, Schlörer N, Kamber M, Schänzer W. Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC-MS/MS. Analytical and Bioanalytical Chemistry. 2008 May;391(1):251-61. PMID 18270691
- ^ http://www.vacansoleildcm.co.uk/nieuws/nikita-novikov-provisionally-suspended-after-possible-breach-of-anti-doping-rules.html
- ^ a b http://www.gtxinc.com/Pipeline/OstarineMK2866.aspx?Sid=4
- ^ http://www.faqs.org/sec-filings/091109/GTX-INC-DE-_10-Q/