SR-9009 (Stenabolic)

SR-9009 (Stenabolic) Research Standard

SR-9009 (Stenabolic) is a synthetic small-molecule ligand of the nuclear receptors REV-ERBα (NR1D1) and REV-ERBβ (NR1D2). Originally characterized as a tool for studying the circadian regulation of lipid metabolism, glucose handling, and mitochondrial gene expression, SR-9009 has become a foundational reference compound in nuclear receptor pharmacology. It functions by increasing the constitutive transcriptional repressor activity of REV-ERB receptors. Given the published literature identifying off-target activity in REV-ERB double-knockout models, SR-9009 is utilized by modern research teams as a pharmacologically complex probe requiring careful experimental design and interpretation.

Technical Specifications

Mechanism of Action & Research Context

SR-9009 modulates the circadian clock and metabolic pathways by binding the ligand-binding domain of REV-ERB receptors.

• Transcriptional Repression: The compound enhances the constitutive repression of target genes (e.g., BMAL1) by REV-ERB receptors, which are themselves core components of the circadian clock and regulators of metabolic gene networks.

• Pharmacological Caveat: Scientific literature, notably Dierickx et al. (2019), has demonstrated that SR-9009 exhibits significant REV-ERB-independent off-target activity. Researchers are advised to utilize SR-9009 as a complex tool compound and consider employing newer, highly selective ligands (e.g., GSK4112, STL1267) for comparative pharmacology studies to ensure specificity.

• Metabolic Modeling: Despite off-target findings, it remains a reference point for investigating the modulation of lipid handling, mitochondrial biogenesis, and glucose metabolism in preclinical research systems.

Research Applications

SR-9009 is a specialized reagent essential for comparative nuclear receptor research.

Primary fields of in vitro laboratory investigation include:

• Circadian Rhythm Studies: Mapping the regulation of core clock genes (BMAL1, CLOCK, PER, CRY) and the impact of REV-ERB signaling on cellular rhythmicity.

• Comparative Pharmacology: Acting as a benchmark alongside emerging REV-ERB ligands to validate binding and transrepression data.

• Metabolic Pathway Research: Investigating the links between REV-ERB signaling and mitochondrial gene expression or lipid metabolism, often compared against PPAR-δ agonists like GW-501516.

• Off-Target Characterization: Utilizing the compound in mechanistic studies to differentiate between REV-ERB-mediated and REV-ERB-independent physiological effects.

Storage & Handling Guidelines

To maintain the chemical stability and experimental reliability of the compound:

• Long-Term Storage: Store in a dry, cool environment. Maintain at -20 °C for extended stability.

• Light Sensitivity: Protect strictly from direct light to prevent degradation of the nitrothiophene moiety.

• Environmental Control: Keep the container tightly sealed to prevent moisture ingress.

• Solubility Note: The compound is soluble in DMSO and polar organic solvents (ethanol, propylene glycol) but demonstrates poor water solubility.

Regulatory & Research Note

SR-9009 is included on the World Anti-Doping Agency (WADA) Prohibited List under the “Metabolic modulators” category (S4.4). It is not approved for any human, veterinary, or clinical use, and all research must be conducted in strict compliance with applicable institutional and legal standards.

Research Use Disclaimer

Research Use Only Disclaimer: This product is developed and distributed strictly as a Research Use Only (RUO) laboratory reference chemical intended exclusively for non-clinical analytical and scientific investigation. It is not an FDA-approved drug, medical treatment, dietary supplement, or food ingredient, and is strictly prohibited for human or animal consumption. Kimera Chems supplies this high-purity research material solely to qualified institutions and professional investigators for authorized laboratory research.