YK11 is known as a myostatin inhibitor. Myostatin is literally a limiting factor for muscle growth, as one of its jobs is to keep muscles from growing too large. Thus, scientists realized that just like other SARMs, this could have applications in the medical world. YK11 is also a myostatin inhibitor (myostatin reduces our muscle mass), which means that you won’t be losing muscle while cutting and will very likely gain some instead, making it a great compound for cutting, lean bulking and especially body recomposition. When it comes to the legality of YK11, it all really comes down to the legality of SARMs. Basically, SARMs are legal to buy and use in every country in the world. The only exception is Australia, we will talk about that later.Everywhere else, however, you don’t have to worry about getting into trouble for using compounds like YK11. Remember, however, that it is only meant for research purposes and isn’t approved for human consumption. The reason YK11 helps build muscle so well is that it blocks Myostatin (a protein that reduces muscle) and shoots up Follistatin levels (Follistatin promotes muscle gain). This results in an incredible ability to increase lean body mass when bulking and preserve your muscle when cutting.

Myostatin inhibitor YK11 as a preventative health supplement

Sepsis is a leading cause of morbidity that adversely affects the biological functions of patients. Severe sepsis can be devastating if not managed rapidly, as it instigates acute respiratory distress syndrome, systematic inflammation, and multiple organ dysfunction known as septic shock. Follistatin (FST), a myostatin and activin-binding protein, has been used as a treatment for several degenerative muscle diseases. (17α,20E)-17,20-[(1-Methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic Acid Methyl Ester (YK11), labeled as the most potent myostatin inhibitor on the market, was first studied in 2011 by the Japanese researcher Yuihi Kanno. YK11 attaches to the androgen receptor to help inhibit the production of myostatin in the muscle, easing the muscle to create more FST, thus, increasing muscle growth.  Herein, we confirmed whether blocking myostatin function by YK11 helps to prevent the muscle loss originally triggered by the inoculation of Escherichia coli and carbapenem-resistant bacteria in animal models of sepsis.[1]

Studies have shown that YK11, a selective androgen receptor myostatin inhibitor, accelerates the expression of FST, cell proliferation, selective regulation of myogenic genes, and mineralization in MC3T3-E1 mouse osteoblasts and C2C12 myoblast cells. However, the clinical effects of YK11 on various diseases have not been reported yet. These effects of YK11 on the inflammatory indicators of sepsis provide new insights into the mechanisms of muscle wasting. Interestingly, the data also showed that muscle mass improved due to FST action as an antagonist of myostatin. The reversal of impaired myogenesis by YK11 via the myostatin signaling pathway in bacterial sepsis revealed in this study advocates a new set of drug targets for clinical intervention in sepsis-induced muscle atrophy. Clinical trials using TLR4 antagonist and TNF-α inhibitor did not show improvement in the mortality of patients with severe sepsis, nor did they investigate their long-term outcomes on muscle function. The results of this study suggest that YK11 may help revert muscle wasting during sepsis and subdue the inflammatory environment, thereby highlighting its potential as a preventive agent for sepsis-related muscle wasting.

YK11 Up-Regulates Osteoblastic Proliferation and Differentiation in MC3T3-E1 Cells

Androgens are key steroidal hormones that play a critical role in the male reproductive system as in prostatic and testicular development. Androgens also show anabolic effects on bone mineral density and skeletal muscle mass. Following nuclear translocation, the AR homodimer binds to androgen responsive elements (AREs) in the enhancer regions of its target genes. We have previously proposed a synthetic steroidal compound, (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (named YK11), as a novel candidate for SARM. This compound has a partial agonistic effect on AR compared to dihydrotestosterone (DHT) as determined by a reporter gene assay. The present study focus on the bone anabolic effect of YK11 on osteoblastic differentiation. The alkaline phosphatase (ALP) activity, cell growth, mineralization, and the mRNA levels of markers for osteoblastic differentiation were assessed in YK11-treated mouse osteoblastic cell line MC3T3-E1.[2]

OPG is an early differentiation marker that is one of the most frequently used markers to demonstrate osteoblast differentiation. OPG is reported to belong to the tumor necrosis factor (TNF) receptor superfamily as a soluble factor that inhibits osteoclast differentiation. In conclusion, we demonstrated that YK11 promoted osteoblast proliferation and differentiation, and increased ALP activity (a marker of osteoblastic maturation) and calcium deposits as stained with alizarin red S (a marker of mineralization). Similar to DHT, this activity may be mediated by the non-genomic action of AR. Thus, YK11 is useful as a potential anabolic SARM for androgen deficiency related diseases in men, such as osteoporosis. It is known that the selectivity of SARMs is different of each. Thus, to investigate for activity of each SARMs is essential. Since YK11 shows unique myogenic differentiation mechanism in C2C12 cells different from DHT and reported SARMs (unpublished observation), YK11 is a novel type of SARMs. This is the first report for the effect of YK11 on different tissue. However, this compound needs to be subjected to further investigations, such as in vivo experiments.

Studies on the in vivo metabolism of the SARM YK11

A steroidal compound was recently detected in a seized black market product and was identified as (17α,20E)-17,20-[(1-methoxyethylidene) bis (oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11). This compound is described to possess selective androgen receptor modulator- and myostatin inhibitor-like properties. As YK11 is an experimental drug candidate and a non-approved substance for humans, scientific data on its metabolism is scarce.  As expected, no intact YK11 was observed in the elimination study urine samples. While the unconjugated metabolites disappeared within 24 hours post-administration, both glucuronidated and sulfated metabolites were traceable for more than 48 hours.[3]

References

[1]Lee SJ, Gharbi A, Shin JE, Jung ID, Park YM. Myostatin inhibitor YK11 as a preventative health supplement for bacterial sepsis. Biochem Biophys Res Commun. 2021 Mar 5;543:1-7. doi: 10.1016/j.bbrc.2021.01.030. Epub 2021 Feb 12. PMID: 33588136.

[2]Yatsu T, Kusakabe T, Kato K, Inouye Y, Nemoto K, Kanno Y. Selective Androgen Receptor Modulator, YK11, Up-Regulates Osteoblastic Proliferation and Differentiation in MC3T3-E1 Cells. Biol Pharm Bull. 2018;41(3):394-398. doi: 10.1248/bpb.b17-00748. PMID: 29491216.

[3]Piper T, Dib J, Putz M, Fussh?ller G, Pop V, Lagojda A, Kuehne D, Geyer H, Sch?nzer W, Thevis M. Studies on the in vivo metabolism of the SARM YK11: Identification and characterization of metabolites potentially useful for doping controls. Drug Test Anal. 2018 Nov;10(11-12):1646-1656. doi: 10.1002/dta.2527. Epub 2018 Nov 18. PMID: 30379415.