 | |
| Clinical data | |
|---|---|
| Other names | PF-05314882; N-(3H-Imidazo(4,5-b)pyridin-2-ylmethyl)-2-fluoro-4-methyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide |
| Routes of administration | By mouth |
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C27H34FN5O2 |
| Molar mass | 479.600 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
MK-0773, also known asPF-05314882, is asteroidal,orally activeselective androgen receptor modulator (SARM) that was under development byMerck andGTx for the treatment ofsarcopenia (loss ofmuscle 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 compoundTFM-4AS-1.[4]
MK-0773 is a4-azasteroid[5] and apotent andselectiveagonist of theandrogen receptor (AR).[1] It binds to the AR with anEC50 of 6.6 nM and is apartial agonist intransactivation modulation of the AR with an IP of 25 nM and Emax of 78% and has aTRAF2 Emaxof 29% and an N/C interaction (virilization-related) counterscreen assay Emax of 2%.[1] That is, it produces promoter activation but induces the N/C interaction almost negligibly.[1] MK-0773 is reportedly four times as potent astestosterone as an agonist of the AR.[2] The drug is selective and does not bind to othersteroid hormone receptors such as theprogesterone receptor orglucocorticoid receptor and shows no significantinhibition of5α-reductase (IC50 > 10 μM).[1] In addition, it is non-aromatizable and hence has no potential forestrogenic effects orside effects, likegynecomastia.[6] MK-0773 had similar effects onlipidmetabolism relative to DHT, including a decrease in totalcholesterol andhigh-density lipoprotein (HDL) of a similar magnitude.[1]
MK-0773 shows tissue-selective androgenic effectsin vivo in animals.[1] It increaseslean body mass with maximalanabolic effects that are approximately 80% of those ofdihydrotestosterone (DHT).[1] However, it had less than 5% of the effect of DHT onuterine weight, about 30 to 50% of the increase ofsebaceous gland area induced by DHT, and increased the weight of theseminal vesicles by 12% of that of DHT at the highest dosage assessed.[4][1] It had similarly reduced effects on theprostate gland.[1] No significant increase ingene expression of six candidategenes related tovirilization was observed.[7] As such, MK-0773 shows a profile of an anabolic SARM with limited effects on sebaceous glands andreproductive 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, theendometrium, 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 toplacebo but this failed to reachstatistical significance.[10][12] MK-0773 has been associated withelevated liver enzymes in clinical studies.[10]
