YK-11 Molecular Structure & Chemistry — Research Reference

YK-11 is a research compound categorized as a steroidal selective androgen receptor modulator (SARM) and a myostatin modulator, primarily investigated for its distinct chemical structure and its observed effects on androgen receptor signaling and myostatin-related pathways in preclinical models. Its intricate molecular architecture, comprising a modified steroidal backbone, presents a fascinating subject for chemists and pharmacologists exploring novel modulators. Research into YK-11 has been extensively documented, with numerous publications indexed on PubMed detailing various aspects of its chemical synthesis, analytical characterization, and biological interactions, alongside several registered studies on ClinicalTrials.gov further exploring its mechanistic attributes in controlled research settings.

As a subject of rigorous scientific inquiry, understanding the precise YK-11 molecular structure & chemistry is paramount for accurate experimental design, interpretation of results, and ensuring the integrity of research findings. This reference aims to provide a comprehensive overview of its chemical identity, synthetic considerations, analytical characterization methods, and physicochemical properties, all framed strictly within the context of research-use-only applications, without implying any human therapeutic utility or safety. Researchers utilize this compound as a tool to investigate cellular and molecular mechanisms, contributing to a broader understanding of complex biological systems.

YK-11: Chemical Nomenclature and Fundamental Structure

YK-11, a prominent compound of interest in anabolic research, possesses a distinctive steroidal framework augmented by novel substituents, classifying it chemically as a synthetic selective androgen receptor modulator (SARM) and myostatin modulator. Its formal chemical nomenclature, adhering to IUPAC guidelines, is (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,9,20-triene-21-carboxylic acid methyl ester. This complex name precisely conveys its steroidal core, specifically a 19-norpregnane derivative, highlighting key unsaturations at the 4, 9, and 20 positions, and the critical methyl ester functionality at position 21. The presence of a 1-methoxyethylidene acetal linkage spanning C17 and C20 is a unique structural feature contributing significantly to its physicochemical and pharmacological profile, distinguishing it from conventional steroidal and non-steroidal SARMs. This meticulous designation is crucial for unambiguous identification and for elucidating structure-activity relationships in comparative research.

The fundamental structure of YK-11 is rooted in a modified steroid skeleton, exhibiting significant deviations from endogenous androgens, which are instrumental in its selective activity profile. At its core, YK-11 maintains a four-ring gonane structure, albeit with the C19 methyl group typically found in testosterone and its derivatives removed (hence ’19-nor’). This modification is common among synthetic anabolic agents, often influencing receptor binding affinity and metabolic stability. The A-ring features a 3-oxo-4-ene system, a characteristic chromophore also present in many natural steroids and synthetic anabolic agents, essential for androgen receptor binding. However, the most striking modification resides in the D-ring and its C17 side chain. Unlike traditional steroids which often possess a 17β-hydroxyl group, YK-11 incorporates a complex acetal structure at C17, which extends into a 20-ene-21-carboxylic acid methyl ester moiety. This elaborate side chain is hypothesized to impart the compound’s unique pharmacological properties, including its reported myostatin modulating effects, by altering interaction with target proteins beyond the androgen receptor alone.

Stereochemistry plays a pivotal role in the biological activity of steroidal compounds, and YK-11 is no exception. The designation (17α,20E) in its IUPAC name denotes specific stereochemical configurations that are crucial for its interaction with biological targets. The 17α-configuration of the acetal linkage is diametrically opposed to the typical 17β-orientation of naturally occurring androgens and many traditional anabolic steroids. This α-orientation is often associated with reduced androgenic activity and altered metabolic pathways in some steroidal compounds, although in YK-11’s case, it is integrated into a unique acetal ring system. The (20E) designation refers to the E-configuration (trans) of the double bond at C20, which is part of the methyl ester side chain. Precise control over these stereochemical centers during synthesis is paramount for producing a research material with consistent biological activity and for avoiding the formation of inactive or potentially confounding isomers. Any deviation in these specific configurations can lead to significant differences in receptor binding, pharmacokinetic profiles, and ultimately, the observed research outcomes, underscoring the necessity of stringent quality control over stereochemical purity.

Advanced Structural Elucidation: Spectroscopic and Chromatographic Characterization

The unequivocal identification and characterization of YK-11, particularly for high-purity research-grade materials, necessitates the application of advanced spectroscopic and chromatographic techniques. Nuclear Magnetic Resonance (NMR) spectroscopy is indispensable, providing detailed information on the carbon-hydrogen framework and connectivity. Proton NMR (¹H NMR) spectra would exhibit characteristic signals for the olefinic protons in the A and C rings, the acetal protons, and the methyl ester group. Carbon-13 NMR (¹³C NMR) further corroborates the presence and environment of each carbon atom, particularly distinguishing between sp², sp³, and carbonyl carbons. Two-dimensional NMR techniques, such as COSY (Correlation Spectroscopy) and HSQC (Heteronuclear Single Quantum Coherence), are invaluable for confirming proton-proton and proton-carbon correlations, respectively, allowing for comprehensive assignment of the complex YK-11 structure and verifying the integrity of its unique acetal and ester functionalities. These methods collectively serve as a robust fingerprint for structural identity.

Mass Spectrometry (MS) is another cornerstone in the structural elucidation of YK-11, especially when coupled with chromatographic separation. High-resolution mass spectrometry (HRMS) provides precise molecular weight determination, allowing for confirmation of the empirical formula. Electrospray Ionization (ESI-MS) or Atmospheric Pressure Chemical Ionization (APCI-MS) are typically employed to generate protonated or deprotonated molecular ions, from which fragmentation patterns can be studied using tandem mass spectrometry (MS/MS). The fragmentation pathways of YK-11 would reveal characteristic cleavages corresponding to the loss of methanol from the methyl ester, specific fragments from the acetal moiety, and scission of the steroidal backbone. This detailed fragmentation data is crucial for confirming the presence of the specific substituents and their connectivity within the YK-11 structure. Furthermore, the absence of unexpected high-mass ions or unusual fragmentation patterns provides strong evidence for the purity and authenticity of the compound, differentiating it from potential synthetic byproducts or degradation products.

Chromatographic techniques, primarily High-Performance Liquid Chromatography (HPLC) and Gas Chromatography-Mass Spectrometry (GC-MS), are fundamental for assessing the purity profile of YK-11. Reverse-phase HPLC (RP-HPLC) with UV detection at a suitable wavelength (e.g., around 230-250 nm, due to the conjugated ketone in the A-ring and the C20 double bond) is the standard method for quantifying YK-11 and detecting related impurities. The development of robust HPLC methods with optimized mobile phases and stationary phases is critical for achieving baseline separation of YK-11 from its synthetic precursors, isomers, and degradation products. For volatile impurities or for orthogonal verification, GC-MS can be employed, although YK-11’s relatively high molecular weight and potential thermal instability might necessitate derivatization for effective GC analysis. Chiral HPLC may also be necessary to confirm the enantiomeric purity, given the multiple chiral centers within the molecule and the potential for isomer formation during synthesis. These chromatographic profiles, ideally supported by comparison with reference standards, provide the quantitative and qualitative data necessary for ensuring the research material meets stringent purity specifications. Researchers should always consult the quality testing documentation, such as a Certificate of Analysis (CoA), to verify the analytical characterization data of their YK-11 research material.

Spectroscopic Fingerprinting Techniques

• Infrared (IR) Spectroscopy: Identifies key functional groups. YK-11 would exhibit strong absorption bands for the C=O stretch of the ketone (A-ring, ~1700-1720 cm⁻¹), the ester carbonyl (~1735-1750 cm⁻¹), C=C stretching for the conjugated double bonds (~1600-1650 cm⁻¹), and C-O stretching from the acetal and ester functionalities.
• Ultraviolet-Visible (UV-Vis) Spectroscopy: Confirms the presence of chromophores. YK-11’s conjugated π-systems (dienone in A-ring, C20 double bond conjugated with ester) would result in characteristic absorption maxima (λ_max), typically in the range of 230-250 nm, providing a rapid method for identification and concentration estimation, subject to matrix effects.

Physicochemical Properties and Their Research Implications

The physicochemical properties of YK-11 profoundly influence its behavior in research settings, affecting its solubility, formulation stability, and ultimately, its observed biological activity in various experimental models. Key properties such as melting point, solubility in different solvents, partition coefficient (Log P), and pKa are fundamental. While specific empirical data for YK-11’s melting point may vary depending on purity, understanding it provides insight into its solid-state stability and suitability for various handling conditions. Solubility is perhaps one of the most critical properties; YK-11, being a steroidal derivative with a complex side chain, is expected to exhibit limited aqueous solubility but good solubility in organic solvents like DMSO, ethanol, or other common laboratory solvents. This low aqueous solubility dictates the need for appropriate solubilizing agents or co-solvents for in vitro cell culture experiments and in vivo administration in animal models, directly impacting experimental design and the reliability of dose delivery. Incorrect solubilization can lead to precipitation, inaccurate dosing, and confounding results.

The lipophilicity of YK-11, typically quantified by its Log P value (octanol-water partition coefficient), is a crucial determinant of its membrane permeability and distribution within biological systems. Given its steroidal nature and the presence of hydrophobic groups, YK-11 is expected to be moderately to highly lipophilic (Log P > 2). This lipophilicity facilitates passive diffusion across biological membranes, including cell membranes, enabling it to reach intracellular targets such as the androgen receptor. However, excessive lipophilicity can also lead to issues such as poor bioavailability in aqueous environments, non-specific binding to plastics or other biomolecules, and potential accumulation in lipid-rich tissues. Researchers must carefully consider YK-11’s lipophilicity when designing experiments, particularly concerning its interaction with cell culture media components, protein binding, and appropriate solvent systems to ensure accurate and reproducible results. Understanding this property is also vital when developing suitable formulations for animal research, where consistent systemic exposure is paramount.

Although YK-11 does not possess easily ionizable acidic or basic groups within its core structure (the ester group is not readily ionizable under physiological conditions), its overall molecular polarity and potential for hydrogen bonding play a significant role. The carbonyl groups (ketone and ester) and ether oxygen atoms in the acetal linkage contribute to its polar surface area, allowing for some interaction with polar environments. The absence of readily ionizable groups means that its solubility and membrane permeability are less dependent on pH changes within typical physiological ranges, which can simplify some aspects of experimental design compared to compounds with ionizable moieties. However, the ester group is susceptible to hydrolysis, a significant degradation pathway that can be influenced by pH, temperature, and the presence of esterases. This susceptibility underscores the importance of controlling these factors during storage and experimental use to maintain the integrity of the research material. For detailed storage guidelines, researchers can refer to the YK-11 storage and handling reference.

Summary of Key Physicochemical Properties

Understanding the interplay of these properties is essential for robust experimental design:

• Molecular Weight: Approximately 430 g/mol, influencing diffusion rates and formulation.
• Solubility: Low in aqueous media, requiring organic co-solvents (e.g., DMSO, ethanol) for dissolution in research applications. Solubility may be enhanced in lipid-based carriers.
• Log P (estimated): Expected to be moderately high (e.g., 3-5), indicating good cell membrane permeability but also potential for non-specific binding and accumulation.
• UV Absorption: Characteristic λ_max due to conjugated chromophores, valuable for analytical quantification and purity assessment.
• Stability: Susceptible to hydrolysis (ester bond), oxidation, and photodegradation, necessitating controlled storage conditions and careful handling.

Synthetic Pathways and Purity Considerations for YK-11 Research Materials

The synthesis of YK-11 involves intricate multi-step organic reactions, typically commencing from readily available steroid precursors. The complexity arises from the need to selectively introduce and modify functional groups while maintaining specific stereochemistry, particularly at the C17 position and the C20 double bond. A common strategy involves selective oxidation and protection of existing hydroxyl groups, followed by the introduction of the unique C17-C21 side chain. This side chain assembly often requires specialized reactions to form the acetal linkage and the conjugated methyl ester, such as Horner-Wadsworth-Emmons or Wittig reactions for olefin formation, followed by esterification. Each synthetic step carries the potential for byproduct formation, including incomplete reaction products, over-reacted species, and diastereomers. Rigorous control of reaction conditions, reagents, and purification techniques at each stage is paramount to minimize these impurities and to ensure the desired YK-11 structure is formed with high yield and selectivity. Any deviation in the synthetic route or purification protocol can significantly impact the quality of the final research material.

Purity is a non-negotiable attribute for research-grade YK-11. The presence of impurities, even in trace amounts, can confound experimental results, leading to misinterpretations of biological activity. Common impurities encountered in YK-11 synthesis can include unreacted starting materials, intermediate compounds from incomplete reactions, side products arising from competing reaction pathways, and stereoisomers. For instance, epimerization at chiral centers or the formation of the undesired (20Z) isomer instead of the (20E) isomer can lead to compounds with significantly altered or entirely absent biological activity. Other potential impurities include oxidation products, particularly if the compound is exposed to air during synthesis or purification, and hydrolysis products if exposed to moisture or extreme pH conditions, which can cleave the ester bond or the acetal linkage. Therefore, comprehensive analytical characterization using techniques such as HPLC-UV/MS, NMR, and HRMS is critical for identifying and quantifying these impurities and confirming the structural integrity of the synthesized YK-11.

To ensure the highest quality of YK-11 research materials, manufacturers must employ sophisticated purification strategies, typically involving multiple chromatographic steps (e.g., flash chromatography, preparative HPLC) followed by recrystallization or lyophilization. Subsequent quality control (QC) is performed on the final bulk material. This QC process involves a battery of analytical tests to confirm the identity, purity, and concentration. Key purity specifications include the total chromatographic purity (e.g., ≥98% by HPLC), the absence of specified individual impurities above a certain threshold, and confirmation of stereochemical integrity. Furthermore, residual solvent analysis (e.g., by GC-FID) is crucial to ensure that levels of solvents used during synthesis and purification are within acceptable limits, as residual solvents can interfere with biological assays. Endotoxin testing may also be necessary for materials intended for cell culture or in vivo animal studies. Researchers should always demand access to detailed Certificate of Analysis (CoA) documents which attest to the rigorous quality control applied to their YK-11 research material, providing transparency and confidence in their experimental results.

Common Impurities and Their Origins

Understanding potential impurities is vital for interpreting research data:

• Synthetic Byproducts:
  • Isomers (e.g., 20Z-isomer, C17 epimers) due to non-selective reactions.
  • Incompletely reacted intermediates from multi-step syntheses.
  • Side products from competing reactions (e.g., undesired eliminations, rearrangements).
• Degradation Products:
  • Hydrolysis products (e.g., carboxylic acid from ester cleavage, acetal hydrolysis) due to moisture or pH.
  • Oxidation products due to exposure to oxygen or light.
  • Polymerization products under harsh conditions.
• Residual Solvents:
  • Trace amounts of organic solvents used in synthesis and purification (e.g., DCM, ethyl acetate, methanol, DMSO).
  • These can interfere with biological assays or exhibit their own toxicities.

Mechanistic Hypotheses: YK-11 as a SARM and Myostatin Modulator

The mechanistic profile of YK-11 is posited to encompass a dual mode of action: acting as a selective androgen receptor modulator (SARM) and exerting effects on myostatin signaling pathways. As a SARM, YK-11 is hypothesized to bind to the androgen receptor (AR) with high affinity, leading to agonistic activity in specific tissues (e.g., muscle and bone) while exhibiting antagonistic or partial agonistic activity in others (e.g., prostate, sebaceous glands). This tissue selectivity is a hallmark of SARMs, differentiating them from conventional anabolic steroids which typically induce widespread androgenic effects. The unique steroidal structure of YK-11, particularly its C17 acetal-ester moiety, is believed to contribute to its differential interaction with the AR binding pocket and subsequent recruitment of co-activator and co-repressor proteins, thereby modulating gene expression in a tissue-specific manner. Research in various *in vitro* models, including reporter gene assays and cellular proliferation studies, aims to delineate its precise AR binding kinetics and transcriptional activities. For a deeper dive into the proposed mechanisms, researchers can consult resources like the YK-11 Mechanism of Action page.

Beyond its interaction with the androgen receptor, YK-11 is notably hypothesized to modulate myostatin signaling. Myostatin (GDF-8) is a potent negative regulator of muscle growth and differentiation, primarily by signaling through the activin type II receptor. Research suggests that YK-11 may interfere with myostatin’s action by increasing the expression of follistatin, a naturally occurring glycoprotein that binds to and neutralizes myostatin, thereby preventing it from interacting with its receptors. This effect, observed in some *in vitro* and *ex vivo* models, positions YK-11 as a compound of significant interest for studies investigating muscle atrophy and regeneration. The precise molecular pathway through which YK-11 upregulates follistatin or otherwise modulates myostatin signaling is still under active investigation, potentially involving direct transcriptional regulation or indirect cellular signaling cascades that ultimately influence myostatin antagonist expression. This proposed dual mechanism, combining AR agonism with myostatin inhibition, distinguishes YK-11 from many other research compounds.

The interplay between its SARM activity and myostatin modulating effects presents a complex mechanistic landscape for YK-11. While AR activation can directly promote protein synthesis and muscle hypertrophy, the simultaneous modulation of myostatin activity could potentially amplify or synergize these effects by reducing a key inhibitory signal for muscle growth. Experimental designs in animal models often aim to dissect these individual contributions, using selective AR antagonists or myostatin inhibitors as controls, to ascertain the relative importance of each pathway. These studies typically involve assessing changes in muscle mass, fiber type, protein synthesis markers, and gene expression profiles related to both androgen signaling and myostatin/follistatin axes. The distinct chemical structure of YK-11, differing from traditional SARMs and known myostatin inhibitors, suggests novel binding interactions and signal transduction pathways that warrant thorough mechanistic investigation to fully understand its biological impact in various research contexts.

Key Mechanistic Hypotheses

• Androgen Receptor Agonism (Tissue Selective):
  • Binds to the androgen receptor (AR) with high affinity.
  • Promotes anabolic pathways in muscle and bone tissue.
  • Exhibits a differential gene expression profile compared to full AR agonists, indicating tissue selectivity.
  • Specific AR-co-regulator recruitment patterns determine tissue-specific effects.
• Myostatin Modulation:
  • Increases the expression of follistatin, a natural myostatin antagonist.
  • Follistatin binds to myostatin, preventing its interaction with activin type II receptors.
  • This leads to a reduction in myostatin’s inhibitory effects on muscle growth.
  • The mechanism for follistatin upregulation is a subject of ongoing research, potentially involving novel signaling pathways.

Analytical Methodologies for Detection, Quantification, and Quality Control

Comprehensive analytical methodologies are indispensable for ensuring the quality, purity, and accurate quantification of YK-11 in research materials and experimental samples. High-Performance Liquid Chromatography (HPLC) coupled with ultraviolet (UV) detection is the workhorse for routine purity assessment and quantification of YK-11. Given YK-11’s conjugated chromophores in the A-ring and the C20 double bond, it exhibits strong UV absorbance, typically monitored at wavelengths such as 230-250 nm. A robust RP-HPLC method involves optimizing the stationary phase (e.g., C18 column) and mobile phase (e.g., gradient elution using acetonitrile/water or methanol/water with a small percentage of acid for peak shape improvement) to achieve excellent resolution between YK-11 and its potential impurities or degradation products. This allows for accurate determination of chromatographic purity, which should be consistently ≥98% for research-grade material, and precise quantification against a certified reference standard.

For enhanced specificity and confirmation of identity, HPLC-Mass Spectrometry (HPLC-MS) is often employed. This technique combines the separation power of HPLC with the molecular specificity of mass spectrometry. HPLC-MS, particularly using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) in positive ion mode, allows for the detection of the protonated molecular ion of YK-11 (e.g., [M+H]⁺ at m/z ~431) and characteristic fragment ions. This is invaluable for identifying co-eluting impurities that may not be distinguishable by UV detection alone and for confirming the structural identity of YK-11 in complex matrices. Tandem mass spectrometry (MS/MS) provides further structural detail through fragmentation patterns, allowing for unambiguous identification of YK-11 and its known degradation products or synthetic impurities. This method is critical for confirming batch-to-batch consistency and for troubleshooting unexpected analytical results, providing a high level of confidence in the material’s integrity.

Beyond routine purity and identity confirmation, several specialized analytical methods contribute to a holistic quality control profile for YK-11. Gas Chromatography-Mass Spectrometry (GC-MS) can be utilized for the detection and quantification of residual organic solvents from the synthesis process, which is crucial as these solvents can interfere with biological assays. For compounds with

Frequently Asked Questions

What is the systematic chemical name for YK-11?

The systematic chemical name for YK-11 is typically described as (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,9,11-triene-21-carboxylic acid methyl ester, though slight variations in nomenclature might exist across different research publications.

How is YK-11 classified in research contexts?

In research contexts, YK-11 is classified as a steroidal selective androgen receptor modulator (SARM) and a myostatin modulator, studied for its unique dual mechanism of action.

What analytical techniques are crucial for confirming YK-11’s structure and purity?

Crucial analytical techniques for confirming YK-11’s structure and purity include Nuclear Magnetic Resonance (NMR) spectroscopy (e.g., 1H, 13C), Mass Spectrometry (MS), High-Performance Liquid Chromatography (HPLC) for purity and quantification, and Infrared (IR) spectroscopy for functional group identification.

Why is the steroidal backbone of YK-11 significant for its research properties?

The steroidal backbone of YK-11 is significant because it provides the foundational scaffold that allows for interactions with androgen receptors, influencing its binding affinity and selectivity characteristics observed in research models, distinguishing it from non-steroidal SARMs.

What are the primary areas of research where YK-11 is utilized?

YK-11 is primarily utilized in research to investigate androgen receptor biology, myostatin signaling pathways, and potential modulation of cellular processes related to muscle and bone metabolism in preclinical *in vitro* and *in vivo* models.

Are there any specific storage considerations for YK-11 research material to maintain its integrity?

To maintain the integrity of YK-11 research material, it is generally recommended to store it in a cool, dark, and dry environment, typically at -20°C, protected from light and moisture, to mitigate degradation pathways such as oxidation and hydrolysis.

How does YK-11’s mechanism as a myostatin modulator differ from its SARM activity in research?

In research, YK-11’s proposed mechanism as a myostatin modulator involves influencing pathways that regulate myostatin, a protein known to limit muscle growth, while its SARM activity relates to its selective binding and activation of androgen receptors in specific tissues, which are distinct yet potentially complementary research avenues.

Can YK-11 be compared to other SARMs or myostatin inhibitors in research?

Yes, YK-11 can be compared to other SARMs or myostatin inhibitors in research to elucidate differences in their chemical structures, receptor binding profiles, tissue selectivity, and mechanistic outcomes, providing valuable insights into structure-activity relationships and pathway modulation.

Scientific References

• PubMed: YK-11
• ClinicalTrials.gov: YK-11

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