Purity: > 98%
Ostarine(cas 841205-47-8), also known as GTx-024 or MK-2866 or enobosarm , is an investigational selective androgen receptor modulator (SARM) for treatment of conditions such as muscle wasting and osteoporosis, formerly under development by Merck & Company. GTx and Merck had clinical development plans to evaluate Ostarine for the treatment of muscle loss in patients with COPD and for the treatment of chronic sarcopenia. They had a goal of initiating an Ostarine Phase II COPD clinical trial in the first quarter of 2010 and an Ostarine Phase IIb chronic sarcopenia clinical trial in 2010.
1. Endocrinology. 2015 Dec;156(12):4522-33. doi: 10.1210/en.2015-1479. Epub 2015 Sep 22.
Enobosarm (GTx-024) Modulates Adult Skeletal Muscle Mass Independently of the Androgen Receptor in the Satellite Cell Lineage.
Dubois V(1), Simitsidellis I(1), Laurent MR(1), Jardi F(1), Saunders PT(1), Vanderschueren D(1), Claessens F(1).
(1)Molecular Endocrinology Laboratory (V.D., M.R.L., F.C.), Department of Cellular and Molecular Medicine, Department of Gerontology and Geriatrics (M.R.L.), and Clinical and Experimental Endocrinology (F.J., D.V.), Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium; and Medical Research Council Centre for Inflammation Research (I.S., P.T.K.S.), University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
Androgens increase skeletal muscle mass, but their clinical use is hampered by a lack of tissue selectivity and subsequent side effects. Selective androgen receptor modulators elicit muscle-anabolic effects while only sparingly affecting reproductive tissues. The selective androgen receptor modulator, GTx-024 (enobosarm), is being investigated for cancer cachexia, sarcopenia, and muscle wasting diseases. Here we investigate the role of muscle androgen receptor (AR) in the anabolic effect of GTx-024. In mice lacking AR in the satellite cell lineage (satARKO), the weight of the androgen-sensitive levator ani muscle was lower but was decreased further upon orchidectomy. GTx-024 was as effective as DHT in restoring levator ani weights to sham levels. Expression of the muscle-specific, androgen-responsive genes S-adenosylmethionine decarboxylase and myostatin was decreased by orchidectomy and restored by GTx-024 and DHT in control mice, whereas the expression was low and unaffected by androgen status in satARKO. In contrast, insulin-like growth factor 1Ea expression was not different between satARKO and control muscle, decreased upon castration, and was restored by DHT and GTx-024 in both genotypes. These data indicate that GTx-024 does not selectively modulate AR in the satellite cell lineage and that cells outside this lineage remain androgen responsive in satARKO muscle. Indeed, residual AR-positive cells were present in satARKO muscle, coexpressing the fibroblast-lineage marker vimentin. AR positive, muscle-resident fibroblasts could therefore be involved in the indirect effects of androgens on muscle. In conclusion, both DHT and GTx-024 target AR pathways in the satellite cell lineage, but cells outside this lineage also contribute to the anabolic effects of androgens.
2. J Cachexia Sarcopenia Muscle. 2011 Sep;2(3):153-161. Epub 2011 Aug 2.
The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial.
Dalton JT(1), Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, Morton RA, Steiner MS.
(1)GTx, Inc., 175 Toyota Plaza, Memphis, TN 38103 USA.
BACKGROUND: Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS: GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION: GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.