YK-11: A Steroidal Androgen Receptor Partial Agonist and the Follistatin Hypothesis

For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.

YK-11 is usually grouped with SARMs, and the researchers who first described it called it a selective androgen receptor modulator. Structurally, however, it is quite different from nearly every other compound in the class. Where Ostarine, LGD-4033 and RAD-140 are nonsteroidal, YK-11 is a steroid: a 19-norpregnane derivative with an unusual orthoester-derived ring system at the D-ring. It is also notable for a proposed mechanism involving follistatin, a protein that binds and neutralizes myostatin, which is why it is sometimes marketed under names such as “Myostine.”

The published literature on YK-11 is small and almost entirely in-vitro and animal-based. This review summarizes what it reports, where the gaps are, and what laboratories should consider. Explicit SARMs supplies YK-11 Myostine Capsules strictly as laboratory reference material.

What Is YK-11?

YK-11 is (17-alpha,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester. [1] It was described by a research group at Toho University in Japan.

• Common names: YK-11, YK11, sold as “Myostine”
• Class: steroidal androgen receptor partial agonist, described by its discoverers as a SARM
• Primary target: androgen receptor
• Proposed downstream mediator: follistatin
• Research setting: cell culture and rodent studies; no human clinical trials
• Regulatory status: not approved by the FDA or any other regulator for any indication

Mechanism of Action

Partial agonism without N/C interaction

The androgen receptor has an amino-terminal domain (NTD) and a carboxyl-terminal ligand-binding domain. When a full agonist such as DHT binds, the two ends of the receptor interact, the N/C interaction, which supports full transcriptional activity at many genes.

In the 2011 paper that introduced YK-11, Kanno and colleagues reported that it acted as a partial agonist in an androgen response element reporter assay, accelerated nuclear translocation of the receptor, and did not induce the N/C interaction. It also blocked DHT-induced N/C interaction. In MDA-MB-453 cells, its effects on gene expression relative to a full agonist varied with the gene, which the authors described as gene-selective agonism. [1]

The follistatin finding

In 2013, the same group studied YK-11 in C2C12 mouse myoblasts, a standard model of muscle cell differentiation. YK-11 induced key myogenic regulatory factors (MyoD, Myf5 and myogenin) more strongly than DHT. YK-11, but not DHT, increased expression of follistatin, and an anti-follistatin antibody reversed the YK-11-induced differentiation. [2] This is the origin of the idea that YK-11 acts partly through follistatin and, indirectly, through myostatin neutralization. It is a cell culture finding and has not been confirmed in controlled in-vivo mechanistic studies.

Bone cells

A 2018 study reported that YK-11 and DHT both increased proliferation and mineralization of MC3T3-E1 mouse osteoblast cells, increased osteoblast markers such as osteoprotegerin and osteocalcin, and increased Akt phosphorylation. These effects were attenuated by an AR antagonist, which supports AR-mediated, partly non-genomic signaling. [3]

Research History

YK-11 was first reported in 2011 [1], followed by the myoblast study in 2013 [2] and the osteoblast study in 2018. [3] Since then, most new publications have come from two directions: anti-doping laboratories studying its metabolism and detection [6][7], and rodent studies examining possible neurological effects. [4][5]

What Published Studies Report

Rodent neurochemistry

Two studies by Dahleh and colleagues in male Wistar rats reported adverse findings in the hippocampus. In a 2023 study, YK-11 administration was associated with increased oxidative stress and impaired markers of mitochondrial function in the hippocampus. [4] A 2024 follow-up reported increased pro-inflammatory cytokines (IL-1-beta and IL-6), reduced IL-10, activation of apoptotic signaling, downregulation of BDNF/TrkB/CREB signaling, and impaired aversive memory consolidation. [5] These are the most detailed in-vivo data on YK-11 and point to the central nervous system as an important area of toxicology research.

Metabolism

Piper and colleagues reported that YK-11 is extensively metabolized, consistent with its labile orthoester-derived structure. In an elimination study with deuterated YK-11, 14 urinary metabolites were detected, and no intact YK-11 was found in urine. Glucuronidated and sulfated metabolites remained detectable for more than 48 hours. [6] A 2024 report from the UCLA Olympic Analytical Laboratory described detection of YK-11 in a doping control sample. [7]

Research Considerations

• Steroid, not a typical SARM. Because YK-11 is steroidal, assumptions about lack of 5-alpha reductase or aromatase metabolism that apply to nonsteroidal SARMs should not be carried over without testing.
• Chemical stability. The orthoester-derived moiety is labile. Protect stock solutions from acid and moisture, prepare fresh solutions where practical, and confirm integrity by LC-MS over the course of a study.
• Follistatin endpoints. To test the follistatin hypothesis in vivo, measure follistatin expression and include neutralizing-antibody or knockdown controls, as in the original cell work. [2]
• Neurological endpoints. Given the rodent hippocampal findings, oxidative stress markers, cytokines and behavioral assays are relevant secondary endpoints. [4][5]
• Small evidence base. Most mechanistic data come from one research group. Independent replication is a priority.

How YK-11 Differs From Nonsteroidal SARMs

YK-11 is often discussed as if it were interchangeable with nonsteroidal SARMs. The literature supports several important differences:

• Structure. YK-11 has a steroid nucleus, while Ostarine, LGD-4033, RAD-140, S4 and S-23 are nonsteroidal.
• Agonist type. YK-11 is described as a partial agonist that does not induce the N/C interaction, while compounds such as S-23 are full agonists in vitro. [1]
• Proposed mediator. The follistatin mechanism reported in C2C12 cells is specific to YK-11 in the published literature. [2]
• Metabolic fate. YK-11 is extensively metabolized, with no intact compound found in urine in the published elimination study, which differs from the more stable nonsteroidal SARMs. [6]
• Evidence base. YK-11 has no human trial data and a small number of primary papers.

These differences mean that results from nonsteroidal SARM studies should not be extrapolated to YK-11.

WADA Status

YK-11 is named explicitly in WADA section S1.2 (Other Anabolic Agents) and is prohibited at all times. Follistatin and other myostatin-binding proteins are separately prohibited under S4.3. [8]

Storage, Purity and COA

• Store capsules sealed, dry, cool and away from light. Moisture is a particular concern given the labile orthoester-derived structure.
• Log lot numbers and receipt dates.
• Review the lot-specific Certificate of Analysis. It should report HPLC purity, confirm identity by mass spectrometry, and list the lot number and analysis date. For a hydrolytically sensitive compound, the analysis date matters; recent testing is more informative than an old certificate.

For lot documentation, use the contact page.

Related Research Compounds

• LGD-4033 Ligandrol Capsules, a nonsteroidal SARM with published phase 1 data
• RAD-140 Testolone Capsules, a nonsteroidal SARM studied in neuroscience and oncology models
• S23 Capsules, a high-affinity aryl-propionamide SARM
• Class overview: SARMs vs Traditional Research Compounds and the SARMs collection

Frequently Asked Questions

Is YK-11 a steroid?

Yes. YK-11 has a steroid backbone (a 19-norpregnane derivative). Its discoverers described it as a SARM because of its partial, gene-selective activity at the androgen receptor. [1]

Is YK-11 a myostatin inhibitor?

Not directly. In C2C12 cells, YK-11 increased follistatin, a protein that binds myostatin, and blocking follistatin reversed its effect on differentiation. [2] That indirect mechanism has not been confirmed in controlled animal studies.

Has YK-11 been tested in humans?

No. There are no registered or published human clinical trials of YK-11.

What safety findings have been published?

Rat studies have reported increased hippocampal oxidative stress, mitochondrial dysfunction, inflammation and impaired memory consolidation. [4][5]

Is YK-11 approved by the FDA?

No. YK-11 has never been approved by the FDA or any other regulator.

Is YK-11 prohibited in sport?

Yes. It is named in WADA section S1.2 and is prohibited at all times. [8]

References

1. Kanno Y, et al. (17-alpha,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. Biol Pharm Bull. 2011. PubMed 21372378
2. Kanno Y, et al. Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression. Biol Pharm Bull. 2013. PubMed 23995658
3. Yatsu T, et al. Selective Androgen Receptor Modulator, YK11, Up-Regulates Osteoblastic Proliferation and Differentiation in MC3T3-E1 Cells. Biol Pharm Bull. 2018. PubMed 29491216
4. Dahleh MMM, et al. YK11 induces oxidative stress and mitochondrial dysfunction in hippocampus: The interplay between a selective androgen receptor modulator (SARM) and exercise. J Steroid Biochem Mol Biol. 2023. PubMed 37468001
5. Dahleh MMM, et al. From gains to gaps? How Selective Androgen Receptor Modulator (SARM) YK11 impact hippocampal function: In silico, in vivo, and ex vivo perspectives. Chem Biol Interact. 2024. PubMed 38521455
6. Piper T, et al. Studies on the in vivo metabolism of the SARM YK11: Identification and characterization of metabolites potentially useful for doping controls. Drug Test Anal. 2018. PubMed 30379415
7. Sobolevsky T, et al. Detection of selective androgen receptor modulator YK-11 in a doping control sample. Drug Test Anal. 2024. PubMed 37946705
8. World Anti-Doping Agency. 2026 Prohibited List. wada-ama.org

For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.