Overview

MK-2866 (Ostarine, Enobosarm) is an arylpropionamide selective androgen receptor modulator (SARM) with well-characterised AR binding affinity data in peer-reviewed literature and documented tissue selectivity profiles in cell-based receptor pharmacology studies. This compound represents a significant advancement in androgen receptor research, offering researchers a valuable tool for investigating selective androgen receptor modulation mechanisms in various in vitro experimental systems.

Molecular Properties

| Property | Value |

|----------|-------|

| Molecular Formula | C₁₉H₁₄F₃N₃O₃ |

| Molecular Weight | 389.33 g/mol |

| CAS Number | 841205-47-8 |

| Class | Arylpropionamide SARM |

The trifluoromethyl substitution pattern and arylpropionamide backbone contribute to MK-2866's distinct pharmacological profile, enabling selective tissue distribution and receptor activation patterns in experimental models.

Androgen Receptor Binding Research

Binding Kinetics and Affinity

MK-2866 demonstrates competitive binding to full-length androgen receptors with a binding affinity (Ki) of approximately 3.8 nM in radioligand displacement assays using [³H]-dihydrotestosterone. The compound exhibits saturable binding kinetics consistent with specific receptor interactions, making it an excellent research tool for androgen receptor binding studies.

Competitive binding experiments reveal that MK-2866 effectively displaces endogenous androgens from AR binding sites, with binding curves following typical sigmoidal dose-response relationships. The compound's binding kinetics show rapid association and relatively slow dissociation rates, indicating stable receptor-ligand complex formation suitable for extended experimental protocols.

Receptor Selectivity Profile

Selectivity screening against a panel of steroid hormone receptors demonstrates MK-2866's preferential binding to androgen receptors over other nuclear hormone receptors. Cross-reactivity studies show minimal binding affinity for estrogen receptors (ERα, ERβ), progesterone receptors, glucocorticoid receptors, and mineralocorticoid receptors at concentrations up to 10 μM, confirming its selectivity profile in receptor binding assays.

Cellular Signalling Pathways

Androgen Receptor Activation

In transfected cell models expressing androgen receptors, MK-2866 functions as a partial agonist, activating AR-mediated transcriptional responses. Luciferase reporter assays using androgen response elements (ARE) demonstrate dose-dependent activation with EC₅₀ values ranging from 10-100 nM depending on cell type and experimental conditions.

The compound induces androgen receptor nuclear translocation and DNA binding, as confirmed through immunofluorescence microscopy and chromatin immunoprecipitation assays. These cellular responses occur within 30 minutes of compound exposure, consistent with classical androgen receptor activation mechanisms.

Transcriptional Modulation

Gene expression profiling studies reveal that MK-2866 selectively modulates androgen-responsive gene transcription in various cell models. The compound upregulates classical androgen target genes while showing distinct expression patterns compared to dihydrotestosterone, reflecting its selective modulator properties.

Real-time PCR analysis demonstrates that MK-2866 increases mRNA levels of androgen-responsive genes including KLK3, TMPRSS2, and NKX3-1 in prostate-derived cell lines, with maximal responses observed at 100 nM concentrations after 24-48 hour treatment periods.

Tissue-Selective Activity

Cell Model Studies

Comparative studies across different cell types reveal tissue-selective activation patterns. In skeletal muscle-derived cell models, MK-2866 demonstrates potent anabolic signalling pathway activation, while showing reduced activity in prostate epithelial cells compared to natural androgens.

Osteoblast cell culture experiments show that MK-2866 enhances alkaline phosphatase activity and mineralisation markers, indicating bone-selective anabolic effects in vitro. These tissue-selective responses make MK-2866 valuable for studying selective androgen receptor modulation mechanisms.

Enzyme Interaction Studies

Metabolic stability assays reveal that MK-2866 undergoes limited phase I metabolism by cytochrome P450 enzymes, with primary metabolic pathways involving hydroxylation and demethylation reactions. The compound shows stability in human liver microsome preparations, with a half-life exceeding 60 minutes under standard incubation conditions.

Research Summary

MK-2866 represents a well-characterised selective androgen receptor modulator with documented binding affinity, selectivity profiles, and tissue-specific activity patterns in vitro. Its robust pharmacological properties, including nanomolar AR binding affinity, selective receptor activation, and tissue-specific transcriptional modulation, make it an invaluable research tool for investigating androgen receptor biology and selective modulation mechanisms. The compound's stability and well-defined cellular responses across multiple experimental systems support its continued use in androgen receptor research applications.

All content is intended for in vitro laboratory research purposes only. Not for human or animal consumption. Not intended to diagnose, treat, cure, or prevent any condition.