MK-0773, also known as PF-05314882, is a steroidal, orally activeselective androgen receptor modulator (SARM) that was under development by Merck and GTx for the treatment of sarcopenia (loss of muscle mass) in women and men.[1][2][3] Clinical trials for sarcopenia began in late 2007 but the collaboration between Merck and GTx ended in early 2010 and GTx terminated development of MK-0773 shortly thereafter.[2] MK-0773 was developed as a more advanced version of the related compound TFM-4AS-1.[4]
MK-0773 shows tissue-selective androgenic effects in vivo in animals.[1] It increases lean body mass with maximal anabolic effects that are approximately 80% of those of dihydrotestosterone (DHT).[1] However, it had less than 5% of the effect of DHT on uterine weight, about 30 to 50% of the increase of sebaceous gland area induced by DHT, and increased the weight of the seminal vesicles by 12% of that of DHT at the highest dosage assessed.[4][1] It had similarly reduced effects on the prostate gland.[1] No significant increase in gene expression of six candidate genes related to virilization was observed.[7] As such, MK-0773 shows a profile of an anabolic SARM with limited effects on sebaceous glands and reproductive tissues in animals and a reduced propensity for virilization.[1]
In human clinical studies, MK-0773 produced anabolism in women and men while producing no or very low effects on sebaceous glands, the endometrium, or the prostate gland after 12 weeks of treatment.[1][7][8][9] A decrease in total cholesterol and HDL was also observed in the clinical studies.[1] MK-0773 produced a significant increase in lean body mass in elderly (≥65 years of age) women with sarcopenia and moderate physical dysfunction.[10][11][12] It also increased muscle strength relative to placebo but this failed to reach statistical significance.[10][12] MK-0773 has been associated with elevated liver enzymes in clinical studies.[10]
^ abZhang X, Sui Z (February 2013). "Deciphering the selective androgen receptor modulators paradigm". Expert Opin Drug Discov. 8 (2): 191–218. doi:10.1517/17460441.2013.741582. PMID23231475.
^Lagojda A, Kuehne D, Krug O, Thomas A, Wigger T, Karst U, et al. (2016). "Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes". European Journal of Mass Spectrometry. 22 (2): 49–59. doi:10.1255/ejms.1415. PMID27419898. S2CID207191784.
^Stoch SA, Friedman EJ, Zhou Y, Zhu H, Larson P, Binkowitz B, et al. (June 2010). "Biomarkers of Bone Metabolism and Serum Free Estradiol (E2) Levels in Medically Castrated Older Men Treated with MK-0773 (MK), Testosterone (T), or Placebo (PBO) for 12 Weeks". Endocrine Reviews. 31 (3): S48.
^Stoch SA, Friedman EJ, Zhu H, Xu Y, Wong P, Chappell DL, et al. (2008). A 12-week pharmacokinetic and pharmacodynamic (PD) study of MK-0773 in healthy postmenopausal (PMP) subjects. The Endocrine Society 90th Annual Meeting, June 12–15, San Francisco, CA. Abst. OR35–33.
^Stoch SA, et al. (2009) 91st Annual Meeting of the Endocrine Society, Washington, D.C. Abst. S21–24.