YK-11 Research Guide: Steroidal SARM Mechanism, the Follistatin Pathway, and Analytical Verification

Most compounds sold as SARMs are non-steroidal molecules designed from scratch to fit the androgen receptor. YK-11 is not one of them. It is a synthetic steroid built on a 19-nor scaffold, with an unusual cyclic orthoester bridging carbons 17 and 20.

That one structural choice explains nearly everything worth knowing about the compound: how it engages the androgen receptor, why it is marketed with a myostatin claim the literature does not quite support, and why it is one of the harder research compounds to verify analytically.

4AminoLabs supplies YK-11 for in vitro and preclinical laboratory work. Everything below summarizes published laboratory findings. Research use only. Not for human or veterinary use.

TL;DR
  • YK-11 is a synthetic steroid that acts as a gene-selective partial agonist of the androgen receptor.
  • Its best-supported muscle-cell effect is follistatin induction, an indirect route to lower myostatin signaling, not direct myostatin inhibition.
  • Rodent studies report hippocampal oxidative stress; no human trial has ever been run.
  • The acid-labile orthoester makes YK-11 degrade in acidic water and behave unusually in mass spectrometry, which changes how a COA should be read.
YK-11 at a glance
430.5
Molecular weight, g/mol
6 of 7
Stereocentres defined
0
Human clinical trials

What YK-11 is

YK-11 was first characterized by Kanno and colleagues at Toho University in 2011. [1] It is sometimes sold under the name “Myostine.”

Identity and physical data

Property Value
Compound YK-11 (YK11, “Myostine”)
CAS number 1370003-76-1
PubChem CID 119058028
Molecular formula C25H34O6
Molecular weight 430.5 g/mol (monoisotopic 430.2355 Da)
InChIKey KCQHQCDHFVGNMK-PQUNLUOYSA-N
Structural class 19-norpregna-4,20-diene steroid with a cyclic orthoester at C-17/C-20
Pharmacological class Steroidal SARM; androgen receptor partial agonist
Human clinical data None
YK-11 chemical structure with the cyclic orthoester ring at C-17/C-20 highlighted, plus callouts for the 19-nor steroid core and 3-keto-delta-4 A-ring
YK-11 structure drawn from PubChem CID 119058028. The shaded orthoester ring is acid-labile, and its central carbon is the one undefined stereocentre.

Why a steroid behaves like a SARM

The 19-nor steroid core

The backbone belongs to the same 19-nor family as nandrolone. That gives YK-11 a steroid-like metabolic fate: its urinary metabolites resemble reduced 19-norpregnane steroids, not the breakdown products of non-steroidal SARMs. [10]

The orthoester

Orthoesters are acid-sensitive. This single group drives YK-11’s hydrolytic instability and its unusual behavior under electrospray ionization. [9] [13]

One undefined stereocentre

YK-11 has seven stereocentres. Six are specified in the PubChem record; the orthoester carbon is not, because the synthesis does not control it. Material can therefore contain closely related diastereomers, which matters when you read a chromatogram.

Steroid or SARM?

Both labels are defensible. Structurally YK-11 is a steroid; functionally it behaves as a selective androgen receptor modulator. For the non-steroidal compounds in the same family, see our Receptor Modulators research library.

Androgen receptor mechanism

A partial agonist

In androgen-responsive reporter assays, YK-11 activated the androgen receptor (AR) but held transactivation below the maximum produced by dihydrotestosterone (DHT). [1]

No N/C interaction

Full androgens such as DHT induce contact between the receptor’s amino-terminal and carboxyl-terminal domains, which maximal transcription requires. YK-11 did not induce this “N/C interaction” and interfered with DHT’s ability to do so. [1]

Why that makes it gene-selective

A receptor activated without the N/C interaction takes a different shape, recruits different coregulators, and switches on a different subset of genes. A 2022 follow-up in MDA-MB-453 cells reported that differential DNA binding and cofactor recruitment likely explain why YK-11 and conventional androgens regulate different targets. [4] YK-11 is best understood as a qualitatively different AR ligand, not simply a weaker one.

The follistatin pathway vs. the “myostatin inhibitor” label

What the 2013 myoblast study showed

In C2C12 mouse myoblasts, YK-11 drove stronger myogenic differentiation than DHT, with greater induction of MyoD, Myf5, and myogenin. It also increased follistatin expression, which DHT did not. Blocking follistatin with a neutralizing antibody reversed the effect. [2]

An indirect chain, not direct inhibition

Follistatin is an endogenous binding protein that neutralizes myostatin. The supported mechanism is therefore YK-11 → AR activation → follistatin upregulation → reduced myostatin signaling. No published study shows YK-11 binding myostatin or blocking its receptor directly, so “myostatin inhibitor” compresses a three-step cell-culture finding into a claim the data do not support.

Diagram of the indirect pathway from YK-11 through androgen receptor activation and follistatin upregulation to reduced myostatin signaling, with no direct YK-11 to myostatin link
The supported route from YK-11 to myostatin runs through the androgen receptor and follistatin. There is no evidence of direct binding.

The one in vivo signal

A 2021 mouse study in a bacterial sepsis model reported lower myostatin protein and improved survival with YK-11. [5] It is a single infection model and should be read in that context.

Osteoblast and non-genomic signaling data

In MC3T3-E1 mouse osteoblast cells, YK-11 accelerated proliferation and mineralization and raised differentiation markers including osteoprotegerin and osteocalcin. An AR antagonist blunted these effects. [3]

The same study reported increased Akt phosphorylation, attributed to rapid, non-genomic AR signaling rather than transcription alone. Taken with the myoblast work, the in vitro picture is consistent: AR-dependent anabolic signaling in muscle and bone cell lineages. None of it has been tested in human tissue.

Preclinical safety signals

Hippocampal oxidative stress (2023)

In rats, YK-11 raised markers of oxidative stress and mitochondrial dysfunction in the hippocampus. Exercise alone was protective in this model, but exercise combined with YK-11 did not prevent the main adverse findings. [6]

Memory and neurotrophic signaling (2024)

A follow-up combining docking, in vivo, and ex vivo work reported altered aversive memory consolidation and reduced BDNF/TrkB/CREB signaling in rat hippocampus. [7]

Class-level liver signal

A 2024 analysis of suspected adverse-event cases involving SARMs as a class found drug-induced liver injury to be the dominant presentation. [8] This is not YK-11-specific, but it is the relevant class context.

These are animal and case-series data and should not be over-read. Still, the absence of human data is not evidence of a benign profile. It is simply an absence.

Metabolism and anti-doping detection

Human metabolism

Researchers at the German Sport University Cologne predicted that the labile orthoester would make YK-11 heavily metabolized, then confirmed it. They identified reduced 19-norpregnane metabolites in urine, confirmed their structures by synthesis and NMR, and found that conjugated forms stayed detectable well after unconjugated species cleared. [10] Those glucuronides now sit in routine screening panels, and a 2024 report documented detection of YK-11 in an actual doping-control sample. [12]

Equine metabolism

An oral administration study in horses detected parent YK-11 plus multiple phase I metabolites. Liver microsome and S9 incubations produced a large set of metabolites that overlapped poorly with what appeared in vivo, a useful caution for anyone using microsomal systems as a stand-in for whole-animal metabolism. [11]

Analytical challenges: reading a YK-11 COA

Mass spectrometry behaves unusually

Under electrospray ionization, protonated YK-11 fragments heavily in the ion source, shedding small neutral pieces from the orthoester region. [9] The intact [M+H]+ ion near m/z 431 can be weak or absent, and validated methods have relied on fragment ions or the sodium adduct [M+Na]+ near m/z 453. [13] A method built only around m/z 431 can under-report or miss YK-11.

The analyte can degrade mid-run

YK-11 hydrolyzes under acidic, aqueous conditions on a timescale of hours. [13] Acidic mobile phases or samples left in aqueous diluent can create degradation peaks that are an artifact of the method, not the material.

A split peak is not automatically an impurity

Because of the undefined orthoester stereocentre, a selective HPLC method may show a doublet or shouldered peak. A single “perfect” peak may simply mean the method cannot resolve the diastereomers.

Schematic electrospray mass spectrum of YK-11 showing a weak protonated ion near m/z 431, a strong sodium adduct near m/z 453, and fragment ions, with notes on hydrolysis and diastereomers
Schematic only. Methods that look for the sodium adduct or fragment ions avoid the weak protonated molecule.

What to look for on a YK-11 certificate

COA element Why it matters for YK-11
Named, independent laboratory Separates supplier claims from third-party results
Lot number matching the product Results apply only to the batch tested
Identity method with ions reported Confirms the lab used ions YK-11 actually produces
HPLC/UHPLC conditions stated Shows whether degradation and diastereomer peaks were handled correctly
Chromatogram included Shows peak shape, not just a summary number
Analysis date Relevant for a hydrolysis-sensitive compound

Review analytical documentation

Check batch-specific certificates and third-party testing standards before selecting research material.

Product quality in the SARM market

A 2017 JAMA study bought 44 products sold online as SARMs and found that only about half contained a SARM at all; many contained unlisted substances, and labeled amounts often did not match contents. [15] A 2021 UK study reached similar conclusions. [16] A 2021 Korean survey detected YK-11 in supplements that did not declare it. [13]

For a compound as analytically awkward as YK-11, the methods behind a certificate matter as much as the purity figure printed on it.

Laboratory handling and stability

Property Detail
Main stability risk Acid-catalyzed hydrolysis of the orthoester
Solid storage Sealed, dry, protected from light, controlled room temperature or below
Stock solutions Organic solvents such as DMSO; avoid acidic aqueous media
Working dilutions Prepare fresh; verify concentration if a stock has been stored
Handling Treat as a potent hormonally active substance; use appropriate PPE

Consult the Safety Data Sheet before handling. 4AminoLabs supplies YK-11 in non-aqueous formats (PEG-400 solution, MCT oil, and solid reference tablets), consistent with its sensitivity to water and acid.

Evidence scorecard

Claim Evidence level Basis
AR partial agonist without N/C interaction Established (in vitro) [1] [4]
Gene-selective transcriptional profile Established (in vitro) [1] [4]
Follistatin induction in myoblasts Established (in vitro, single model) [2]
Osteoblast proliferation and differentiation Established (in vitro, single model) [3]
Reduced myostatin protein in vivo Preliminary (one mouse sepsis model) [5]
Hippocampal oxidative stress and memory effects Preliminary (rat studies) [6] [7]
Direct myostatin inhibition Not supported No binding or direct-inhibition data
Any effect or safety profile in humans Not established No human trials

Regulatory status

YK-11 has never been approved by any regulatory agency for any indication, and no human clinical trial has been conducted. The World Anti-Doping Agency prohibits it in and out of competition under S1, Anabolic Agents. [14] The U.S. FDA treats SARMs as unapproved drugs, not dietary supplements, and has warned about serious adverse events in this class. [17]

Frequently asked questions

Is YK-11 a SARM or a steroid?

Both labels are accurate in different senses. Structurally, YK-11 is a synthetic steroid built on a 19-norpregnadiene core. Functionally, it acts as a selective, partial agonist of the androgen receptor, which is why it is grouped with SARMs.

Does YK-11 inhibit myostatin?

Not directly. The published mechanism is androgen receptor-mediated induction of follistatin, a protein that neutralizes myostatin. One mouse sepsis study reported lower myostatin protein levels, but no study has shown YK-11 binding or directly inhibiting myostatin.

Has YK-11 been studied in humans?

No. No human clinical trial of YK-11 has been registered or published. All efficacy and safety data come from cell culture and animal models.

Why might a YK-11 chromatogram show two peaks?

The orthoester carbon in YK-11 is not stereochemically controlled during synthesis, so the material can contain closely related diastereomers that a selective HPLC method may partially resolve. Degradation from acidic or aqueous conditions during analysis can also create extra peaks.

Why is YK-11 hard to detect by mass spectrometry?

Under electrospray ionization, protonated YK-11 fragments heavily in the ion source, so the intact protonated molecule can be weak or absent. Reliable methods use the sodium adduct or characteristic fragment ions instead.

How is YK-11 detected in anti-doping tests?

Laboratories target its conjugated urinary metabolites, which remain detectable longer than the parent compound. These metabolites have been incorporated into routine anabolic agent screening.

References

  1. Kanno Y, et al. YK11 is a partial agonist of the androgen receptor. Biol Pharm Bull. 2011;34(3):318-323.
  2. Kanno Y, et al. Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression. Biol Pharm Bull. 2013;36(9):1460-1465.
  3. Yatsu T, et al. Selective androgen receptor modulator, YK11, up-regulates osteoblastic proliferation and differentiation in MC3T3-E1 cells. Biol Pharm Bull. 2018;41(3):394-398.
  4. Kanno Y, et al. Differential DNA-binding and cofactor recruitment are possible determinants of the synthetic steroid YK11-dependent gene expression by androgen receptor in breast cancer MDA-MB-453 cells. Exp Cell Res. 2022.
  5. Lee SJ, et al. Myostatin inhibitor YK11 as a preventative health supplement for bacterial sepsis. Biochem Biophys Res Commun. 2021;543:1-7.
  6. Dahleh MMM, et al. YK11 induces oxidative stress and mitochondrial dysfunction in hippocampus. J Steroid Biochem Mol Biol. 2023;233:106364.
  7. Dahleh MMM, et al. From gains to gaps? How SARM YK11 impacts hippocampal function. Chem Biol Interact. 2024.
  8. Leciejewska N, et al. Selective androgen receptor modulator use and related adverse events including drug-induced liver injury. Eur J Clin Pharmacol. 2024;80(2):185-202.
  9. Thevis M, et al. Mass spectrometric characterization of the SARM YK-11 for doping control purposes. Rapid Commun Mass Spectrom. 2017;31(14):1175-1183.
  10. Piper T, et al. Studies on the in vivo metabolism of the SARM YK11. Drug Test Anal. 2018;10(11-12):1646-1656.
  11. Harding C, et al. Equine metabolism of the SARM YK-11 in urine and plasma following oral administration. Drug Test Anal. 2023.
  12. Sobolevsky T, et al. Detection of selective androgen receptor modulator YK-11 in a doping control sample. Drug Test Anal. 2024.
  13. Lee JH, et al. Development and validation of an LC-MS/MS method for screening six SARMs in dietary supplements. Food Addit Contam Part A. 2021.
  14. World Anti-Doping Agency. Prohibited List, S1 Anabolic Agents.
  15. Van Wagoner RM, et al. Chemical composition and labeling of substances marketed as selective androgen receptor modulators and sold via the internet. JAMA. 2017;318(20):2004-2010.
  16. Leaney AE, et al. Analysis of supplements available to UK consumers purporting to contain SARMs. Drug Test Anal. 2021;13(1):122-127.
  17. U.S. Food and Drug Administration. Certain bodybuilding products put consumers at risk for heart attack, stroke, serious liver damage and more.

Research use only. All products supplied by 4AminoLabs are intended strictly for laboratory research. They are not drugs, dietary supplements, food, cosmetics, or veterinary products, and are not for human or animal consumption. Nothing here is dosing guidance or a therapeutic claim.

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