SR-9011

SR-9011 (REV-ERB Agonist) Research Standard

SR-9011 is a synthetic small-molecule ligand of the nuclear receptors REV-ERBα (NR1D1) and REV-ERBβ (NR1D2). Developed as a structural analog of SR-9009, SR-9011 demonstrates improved in vivo pharmacokinetics, including enhanced bioavailability and brain exposure in preclinical models. In laboratory research, it serves as a foundational reference compound for probing the REV-ERB-mediated regulation of circadian rhythm, mitochondrial gene expression, and lipid metabolism. Due to its well-documented role in academic literature—and the subsequent characterization of off-target pharmacological activity—SR-9011 is utilized as a complex tool compound requiring meticulous experimental design.

Technical Specifications

Mechanism of Action & Research Context

SR-9011 functions by binding the ligand-binding domain of REV-ERBα and REV-ERBβ, driving the constitutive transcriptional repression of downstream target genes.

• Circadian Regulation: The compound modulates the expression of core clock genes, such as BMAL1 and CLOCK. It is frequently used in experiments to perturb or phase-shift circadian rhythm gene expression in hypothalamic, hepatic, and muscular tissues.

• Pharmacokinetic Advantage: Unlike its predecessor SR-9009, SR-9011 exhibits significantly improved pharmacokinetic properties, making it the preferred chemical probe for in vivo research where systemic exposure is a critical variable.

• Pharmacological Caveats: Research by Dierickx et al. (2019) demonstrated that many physiological effects observed with SR-class compounds are reproducible in REV-ERB double-knockout models. Consequently, researchers must interpret SR-9011 data with an understanding of its potential REV-ERB-independent off-target activity. Comparative studies using highly selective ligands (e.g., GSK4112, STL1267) are often recommended for specificity validation.

Research Applications

SR-9011 is a specialized reagent essential for comparative nuclear receptor pharmacology and chronobiology.

Primary fields of in vitro and in vivo laboratory investigation include:

• Circadian Clock Gene Mapping: Investigating the modulation of rhythmic gene networks in diverse tissue types.

• Comparative ADME Research: Utilizing the compound’s superior pharmacokinetic profile for comparative studies alongside SR-9009 to assess the impact of structural modifications (N-pentyl carboxamide vs. ethyl carbamate).

• Metabolic Pathway Signaling: Evaluating the influence of REV-ERB agonism on mitochondrial gene expression, glucose handling, and lipid oxidation.

• Off-Target Pharmacology: Characterizing the compound’s non-specific effects to advance the development of next-generation, high-selectivity REV-ERB ligands.

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 but demonstrates poor water solubility.

Regulatory & Research Note

SR-9011 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.