YK-11 is a synthetic SARM that is a gene-selective partial agonist of the androgen receptor. It was first studied in Japan in 2011 by researcher Yuichiro Kanno. YK-11 accelerates the translocation of the androgen receptor into the nuclear compartment where its amino-terminal domain (NTD) functions as a constitutive activator of androgen receptor target genes . It does not however induce amino/carboxyl-terminal (N/C) interaction that is required for full transactivation of the androgen receptor.
YK-11 acts as a gene-specific agonist of the androgen receptor in MDA-MB 453 cells as well. YK-11 has shown greater anabolic activity in vitro in C2C12 myoblasts than DHT [1, 2]. YK-11 promoted a cascade of key myogenic regulatory factors in skeletal muscle tissue such as myogenic differentiation factor (MyoD), myogenic factor 5 (Myf5), to a significantly greater extent than DHT. This can in part explain why YK-11 exerts its selective modulation of the androgen receptor.
What really sets YK-11 apart is that a key component of its anabolic activity is modulated via expression of follistatin. They discovered this by co-administering anti-follistatin antibodies with YK-11 to measure the difference in effects . Follistatin has been shown to promote insulin-stimulated glucose and amino acid uptake into skeletal muscle cells, improving insulin sensitivity directly and increasing skeletal muscle mass . Follistatin proteins also block inhibitory ligands from binding to Transforming Growth Factor-ß . Perhaps the most alluring effect of follistatin is binding and neutralizing of catabolic proteins Activin A, Activin B, and Myostatin. Unfortunately follistatin proteins themselves undergo rapid proteolysis and have limited bioavailability and half-life even when injected directly into a wasting muscle. YK-11 however stimulates the body to produce more follistatin proteins systemically and locally which may circumvent this shortfall of direct follistatin administration [2, 4].
What Are the Benefits of YK-11?
1. Rapidly increases muscle mass via pathways that other steroids/SARMs do not modulate.
2. Activates Follistatin and inhibits Myostatin genes
3. Does not exert androgenic effects in target tissues
1. Kanno Y, Hikosaka R, Zhang SY, Inoue Y, Nakahama T, Kato K, Yamaguchi A, Tominaga N, Kohra S, Arizono K, Inouye Y (2011). “(17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11) is a partial agonist of the androgen receptor”. Biological & Pharmaceutical Bulletin. 34 (3): 318–23. PMID 21372378
2. Kanno Y, Ota R, Someya K, Kusakabe T, Kato K, Inouye Y (2013). “Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression”. Biological & Pharmaceutical Bulletin. 36 (9): 1460–5. PMID 23995658.
3. Han X, Moller LLV, et al. Mechanisms involved in follistatin-induced hypertrophy and increased insulin action in skeletal muscle. J Cachexia Sarcopenia Muscle. 2019 Aug 11. doi: 10.1002/jcsm.12474.
4. Castonguay R, Lachey J, Wallner S, et al. Follistatin-288-Fc Fusion Protein Promotes Localized Growth of Skeletal Muscle. J Pharmacol Exp Ther. 2019 Mar;368(3):435-445. doi: 10.1124/jpet.118.252304. Epub 2018 Dec 18.