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YK11: a SARM and myostatin inhibitor in one

Japanese researchers are doing experiments with a new SARM which, if the first publications are anything to go by, has a stronger anabolic effect than classic steroids such as DHT. YK11 attaches itself to the androgen receptor, causes few androgen effects and inhibits – the researchers haven’t quite worked out how – the effect of myostatin.
Japanese researchers are doing experiments with a new SARM which, if the first publications are anything to go by, has a stronger anabolic effect than classic steroids such as DHT. YK11 attaches itself to the androgen receptor, causes few androgen effects and inhibits – the researchers haven’t quite worked out how – the effect of myostatin.

The structure of YK11 is shown above. Click on the illustration, and a larger version will appear. It’s a strange molecule, probably made by merry chemists under the influence of self-brewed ethanol and then forgotten. The Japanese found it when they were screening compounds for androgenic properties. Its full name is (17-alpha,20E) 17,20-[(1-methoxyethylidene)bis(oxy)] 3-oxo-19-norpregna-4,20-diene 21-carboxylic acid methyl ester.

There are only two studies on YK11 on PubMed. [PubMed: YK11] But the researchers are funded by a prestigious Japanese government fund for young and promising talent. And if you get money from an institution like that you’re unlikely to stop at two publications. We wager we’ll be hearing more about YK11 in the not-too-distant future.

In 2011 Yuichiro Kanno of Toho University published the results of a preliminary study of YK11, in which he demonstrated that the unusual compound was a SARM. [Biol Pharm Bull. 2011; 34(3): 318-23.] YK11 attaches itself to the androgen receptor, but only initiates processes that lead to the classic side effects of androgens – such as growth of body hair, increased aggression and growth of the prostate – to a limited extent.

Most SARMs have relatively few androgenic side effects, but often only relatively little anabolic effect – when compared with a substance like testosterone. It seems that this is not the case for YK11, Yuichiro Kanno reported in 2013 in Biological and Pharmaceutical Bulletin. [Biol Pharm Bull. 2013; 36(9): 1460-5.]

In that study Kanno experimented with C2C12-muscle cells, and not with lab animals or humans. Nevertheless Biological and Pharmaceutical Bulletin deemed Kanno’s article interesting enough to publish it as a ‘Highlighted Paper selected by the Editor-in-Chief’. We’re not surprised. Kanno discovered that muscle cells manufacture more anabolic factors if you expose them to 500 nanomoles YK11 than if you expose the same muscle cells to 500 nanomoles DHT.

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Look at the evidence above: YK11 causes a larger increase in the synthesis of Myf5, MyoD and myogenin than DHT does. Myf5, MyoD and myogenin are signal proteins that induce muscles to grow.

The figure below shows how that happens: YK11 induces muscle cells to make more follistatin – much more than DHT does. Follistatin is a strong myostatin inhibitor.

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When the researchers deactivated the androgen receptor, YK11 lost its anabolic effect. So YK11 works via the androgen receptor. When the researchers deactivated follistatin, the anabolic effect disappeared too. Ergo: YK11 is a SARM and a myostatin inhibitor.

By the way, good old testosterone also stimulates the synthesis of follistatin. [Endocrinology. 2009 Mar; 150(3): 1259-68.] So maybe YK11 is a substance that’s as good a muscle strengthener as testosterone, but without the side effects.

“YK11 was shown to be an appropriate anabolic SARM”, the researchers write. “However, further investigation is required to elucidate the mechanisms of the differential activation of the follistatin pathway by YK11 and DHT.”

Selective Androgen Receptor Modulator, YK11, Regulates Myogenic Differentiation of C2C12 Myoblasts by Follistatin Expression.

Kanno Y, Ota R, Someya K, Kusakabe T, Kato K, Inouye Y.

Source

Faculty of Pharmaceutical Sciences, Toho University.

Abstract

The myogenic differentiation of C2C12 myoblast cells is induced by the novel androgen receptor (AR) partial agonist, (17?,20E)-17,20-[(1-methoxyethylidene)bis-(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), as well as by dihydrotestosterone (DHT). YK11 is a selective androgen receptor modulator (SARM), which activates AR without the N/C interaction. In this study, we further investigated the mechanism by which YK11 induces myogenic differentiation of C2C12 cells. The induction of key myogenic regulatory factors (MRFs), such as myogenic differentiation factor (MyoD), myogenic factor 5 (Myf5) and myogenin, was more significant in the presence of YK11 than in the presence of DHT. YK11 treatment of C2C12 cells, but not DHT, induced the expression of follistatin (Fst), and the YK11-mediated myogenic differentiation was reversed by anti-Fst antibody. These results suggest that the induction of Fst is important for the anabolic effect of YK11.

PMID: 23995658 [PubMed – in process]

Source: http://www.ncbi.nlm.nih.gov/pubmed/23995658

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