MK-386
Chemical compound
From Wikipedia, the free encyclopedia
MK-386, also known as 4,7β-dimethyl-4-aza-5α-cholestan-3-one, is a synthetic, steroidal 5α-reductase inhibitor which was first reported in 1994 and was never marketed.[1][2] It is a 4-azasteroid and a potent and selective inhibitor of 5α-reductase type I and shows high selectivity for inhibition of human 5α-reductase type I over 5α-reductase type II, with IC50 values of 0.9 nM and 154 nM, respectively.[2][3] The drug was under investigation for potential treatment of androgen-dependent conditions such as acne and pattern hair loss (androgenic alopecia or baldness), but was discontinued in early clinical trials due to observations of hepatotoxicity such as elevated liver enzymes.[4]
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| Other names | L-733692; 4,7β-Dimethyl-4-aza-5α-cholestan-3-one[1] |
| Routes of administration | By mouth |
| Drug class | 5α-Reductase inhibitor |
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| Formula | C28H49NO |
| Molar mass | 415.706 g·mol−1 |
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MK-386 has been found to decrease circulating concentrations of dihydrotestosterone (DHT) in men by 20 to 30%,[5] which is in accordance with the fact that 5α-reductase type II is responsible for 70 to 80% of DHT production while 5α-reductase type I is responsible for 20 to 30%.[6] In contrast to MK-386, the selective 5α-reductase type II inhibitor finasteride has been found to decrease DHT levels by about 70%, while the non-selective 5α-reductase inhibitor dutasteride decreases DHT levels by up to 98%.[7] Co-administration of MK-386 and finasteride was found to produce near-complete (~95%) suppression of circulating DHT levels.[8]
MK-386 has been found to significantly decrease concentrations of DHT in sebum, similarly to the selective 5α-reductase type II inhibitor finasteride.[9] However, whereas finasteride results in only a modest reduction in sebum DHT levels of 15%, MK-386 has been found to produce a significantly greater reduction of 55%.[9] While finasteride decreases semen DHT levels by approximately 88%, MK-386 has been found to have no effect on levels of DHT in semen.[9] These findings are in accordance with the known tissue distribution of 5α-reductase isoforms.[10]
MK-386 was assessed in the treatment of acne but failed to separate from placebo in effectiveness and was significantly inferior to antibiotic therapy with minocycline.[11][12] In addition, the addition of MK-386 to minocycline failed to increase effectiveness relative to minocycline alone.[11][12] A study of MK-386 treatment for one year in stumptail macaques found that the drug failed to increase scalp hair weight in a model of androgenic alopecia, in contrast to finasteride.[13][14]