Description
Summary Abstract
YK-11 (CAS 1370003-76-1; methyl (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylate) is a steroidal, synthetic selective androgen receptor modulator (SARM) structurally derived from dihydrotestosterone (DHT). Unlike classical SARMs, YK-11 exerts its anabolic effects through two concurrent mechanisms: partial agonism of the androgen receptor (AR) and robust upregulation of follistatin (FST), an endogenous antagonist of myostatin — the principal negative regulator of skeletal muscle growth. YK-11 is the only known SARM that potently induces follistatin-driven myostatin inhibition, positioning it as a research tool for skeletal muscle hypertrophy, satellite cell activation, and androgen signaling studies. Its steroidal scaffold and 17α-methyl group confer oral bioavailability and, notably, significant brain penetrance as demonstrated by physiologically based pharmacokinetic (PBPK) modeling.
Clinical Indications
YK-11 is primarily investigated in skeletal muscle and bone biology contexts:
- Skeletal muscle hypertrophy and sarcopenia research: YK-11 induces myogenic differentiation in C2C12 cells via AR-dependent follistatin induction, increasing myosin heavy chain (MyHC) expression and myotube formation; relevant to sarcopenia, muscle wasting disease, and cachexia models.
- Myostatin pathway inhibition: Follistatin upregulation by YK-11 inhibits the TGF-β superfamily member myostatin at the autocrine level, effectively removing the myostatin brake on satellite cell activation and muscle fiber growth without the immunogenicity of anti-myostatin antibodies.
- Bone metabolism: As an AR agonist with DHT-derived structural homology, YK-11 activates androgen-responsive bone gene expression (including FGF18) and is studied in models of androgen-deficiency–related bone loss and osteoblast differentiation.
Contraindications
- Hepatotoxicity risk: The 17α-methylated steroidal structure confers oral bioavailability but also introduces potential hepatic stress; liver enzyme monitoring is indicated in chronic-exposure research protocols.
- Androgen-sensitive neoplasm models: As an AR partial agonist, YK-11 is contraindicated in models where AR-dependent cell growth would be an uncontrolled variable, including prostate cancer cell line work without appropriate experimental justification.
- Endocrine suppression in male models: Partial AR agonism will compete with endogenous testosterone and DHT for receptor occupancy; HPG-axis (hypothalamic-pituitary-gonadal axis) suppression is expected in chronic-administration models and must be controlled for in hormonal endpoint studies.
Mechanism of Action (MOA)
YK-11’s anabolic effects arise from a dual mechanism distinguishing it from all other known SARMs:
Androgen Receptor Partial Agonism
YK-11 binds the ligand-binding domain (LBD) of the androgen receptor with structural homology to DHT. Unlike DHT, YK-11 does not induce the N-terminal domain/AF1 to LBD/AF2 N/C interaction required for full AR transactivation, resulting in selective, partial AR activation. This tissue-selective agonism stimulates anabolic gene programs (FKBP51, FGF18 at 10 μM) while limiting full androgenic side effect profiles.
Follistatin Induction and Myostatin Inhibition
YK-11 uniquely induces follistatin (FST) mRNA expression in an AR-dependent manner — an effect not observed with DHT at equivalent concentrations. Follistatin is a potent endogenous antagonist of myostatin (GDF-8), binding it with high affinity and preventing its TGF-β receptor engagement. By suppressing myostatin, YK-11 removes the primary brake on satellite cell activation and muscle fiber hypertrophy, enabling anabolic responses beyond the ceiling imposed by endogenous androgens alone.
Myogenic Differentiation Activation
In C2C12 myoblast cultures, YK-11 promotes expression of myogenic regulatory factors (MRFs) including MyoD, myogenin, and MyHC, accelerating myogenic differentiation and myotube formation. These effects are AR-dependent (blocked by AR antagonists) but partially independent of the classical N/C interaction pathway.
5α-Reductase Type II Inhibition and CNS Penetrance
PBPK modeling and molecular docking analyses indicate that YK-11 has remarkable brain permeability and inhibitory activity at 5α-reductase type II (5αR2). This CNS penetrance may be relevant to androgen-mediated neurological research and implies potential neuroendocrine activity beyond peripheral muscle and bone.
Key Features & Specifications
YK-11 is the only SARM known to combine AR partial agonism with direct follistatin induction for dual anabolic signaling:
Chemical Analysis
| Property | Specification Reference Data |
|---|---|
| IUPAC Name | methyl (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylate |
| CAS Number | 1370003-76-1 |
| Molecular Formula | C25H34O6 |
| Molecular Weight | 430.5 g/mol |
| PubChem CID | 119058028 |
| Synonyms | YK11, YK-11 cpd; (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester |
| Form / Variation | 5 MG Capsules — C-042 ($64.00) / 10 MG/mL Liquid 30 mL — L-011 ($54.00) / 50 MG/mL Oil 10 mL — V-010 ($84.00) |
Storage, Safety, and Handling
Storage Protocol
Capsules and liquid: store at controlled room temperature (15–25 °C) away from light and moisture. Oil formulation (V-010): store at 2–8 °C or room temperature in a sealed amber vial; avoid freeze-thaw cycling. All formulations should be protected from UV exposure to prevent photodegradation of the steroidal chromophore.
Handling & Compliance
Handle with standard laboratory PPE. YK-11 is prohibited in competitive athletics under WADA S1 (Anabolic Agents) and relevant anti-doping frameworks. As a steroidal compound with potential HPG-axis effects, institutional review board (IRB) and institutional animal care and use committee (IACUC) compliance is essential for in vivo research protocols.