SR-9009 (Stenabolic) Overview
SR-9009, also known as Stenabolic and as REV-ERB Agonist II, is a synthetic small-molecule ligand of the nuclear receptors REV-ERBα (NR1D1) and REV-ERBβ (NR1D2). It was originally developed at the Scripps Research Institute (Burris laboratory) and characterized in the 2012 Solt et al. Nature paper as a tool compound for investigating REV-ERB-mediated regulation of circadian rhythm, lipid metabolism, glucose handling, and mitochondrial gene expression.
In published in vitro reporter assays, SR-9009 has been characterized with IC₅₀ values of approximately 670 nM at REV-ERBα and 800 nM at REV-ERBβ, where it acts to increase the constitutive transcriptional repressor activity of the receptors. It is widely cited in circadian biology and nuclear receptor pharmacology research as a chemical probe for REV-ERB pathway investigation.
SR-9009 is not approved for human or veterinary use and is supplied strictly for laboratory and analytical research purposes.
Mechanism of Action (Research Context)
SR-9009 binds the ligand-binding domain of REV-ERBα/β and increases the constitutive transcriptional repressor activity of these nuclear receptors. REV-ERB receptors function as transcriptional repressors of core circadian clock genes (notably BMAL1 / ARNTL) and of genes governing lipid metabolism, mitochondrial biogenesis, and inflammatory signaling.
Reported in vitro and preclinical characterizations include:
- IC₅₀ ≈ 670 nM at REV-ERBα; IC₅₀ ≈ 800 nM at REV-ERBβ in chimeric Gal4-LBD reporter systems
- Suppression of BMAL1 mRNA expression in REV-ERB-dependent cell models
- Modulation of circadian gene expression patterns in published rodent studies
- Effects on lipid handling, glucose metabolism, and mitochondrial gene expression observed in early preclinical work (Solt et al. 2012)
Research Background: Off-Target Activity and PK Considerations
Subsequent published research has substantially refined the original characterization of SR-9009 as a clean REV-ERB pharmacological probe. Dierickx et al. (2019, PNAS) reported that SR-9009 has very limited oral bioavailability and that multiple effects originally attributed to REV-ERB engagement are reproduced in REV-ERBα/β double-knockout mice — indicating substantial off-target activity independent of the nominal target receptors. This published off-target finding constrains SR-9009’s utility as a selective REV-ERB tool compound and is a relevant consideration in experimental design and interpretation. Researchers working with REV-ERB pharmacology may also reference newer or alternative REV-ERB ligands (GSK4112, STL1267, and related compounds) for comparative pharmacology work.
This published pharmacological caveat is part of the scientific record on SR-9009 and reinforces the compound’s positioning as a research reagent rather than a definitive therapeutic or performance-related agent.
Chemical Structure & Identification
- Chemical Name: Ethyl 3-[[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]methyl]pyrrolidine-1-carboxylate
- Synonyms: SR-9009; SR9009; Stenabolic; REV-ERB Agonist II
- Chemical Class: Synthetic nuclear receptor ligand — REV-ERBα/β agonist
- CAS Number: 1379686-30-2
- Molecular Formula: C₂₀H₂₄ClN₃O₄S
- Molecular Weight (average): 437.94 g/mol
- Exact Mass (monoisotopic): 437.1176 g/mol
- PubChem CID: 71650462
- UNII: X5DCA09N30
Structural Description: SR-9009 is a small-molecule, non-steroidal nuclear receptor ligand built around a 1-pyrrolidinecarboxylic acid ethyl ester core with a tertiary amine linker bearing two distinct aromatic arms — a 4-chlorobenzyl group and a 5-nitrothiophen-2-ylmethyl group. The 5-nitrothiophene moiety, the tertiary amine, and the pyrrolidine carbamate functionality are key structural features distinguishing SR-9009 from other nuclear receptor ligand chemical classes. Structural identification and molecular data are referenced against PubChem.
Physical and Chemical Properties
- Appearance: White to off-white solid
- Solubility: Soluble in DMSO and polar organic solvents (ethanol, propylene glycol); poorly soluble in water
- Stability: Stable under dry, cool, light-protected storage conditions
- Recommended storage: -20 °C for long-term stability
Research Focus Areas
SR-9009 is commonly referenced in laboratory research involving:
- REV-ERBα/β nuclear receptor binding, transactivation, and transrepression studies
- Circadian rhythm and clock-gene regulation research (BMAL1, CLOCK, PER, CRY pathway studies)
- Comparative nuclear receptor pharmacology across the REV-ERB ligand class (alongside GSK4112, STL1267, and related compounds)
- Lipid metabolism and mitochondrial gene expression signaling research
- Off-target pharmacology characterization (in light of published REV-ERB-independent activity)
- Analytical method development and reference-standard work in anti-doping analytical literature
- Comparative studies with PPAR-δ agonists (GW-501516, GW-0742) and other metabolic-pathway research compounds
Research Background & Regulatory Context
SR-9009 is included on the World Anti-Doping Agency (WADA) Prohibited List under the “Metabolic modulators” category (S4.4). The U.S. Food and Drug Administration has issued public consumer advisories naming SR-9009 and related metabolic research compounds in the context of unapproved bodybuilding and dietary supplement products. This published regulatory and analytical record is part of the scientific literature on the compound and reinforces that SR-9009 is supplied strictly as a research reagent for laboratory and analytical use, not for any therapeutic, performance, dietary supplement, or other consumer application.
Research Use Disclaimer
SR-9009 is intended strictly for laboratory research use only (RUO). Not for human consumption, clinical use, veterinary use, therapeutic application, dietary supplement use, or diagnostic purposes. All handling and use must comply with applicable federal, state, and local laws and institutional laboratory safety standards.
Summary
SR-9009 (Stenabolic) is a structurally defined synthetic REV-ERBα/β nuclear receptor ligand originally developed as a chemical probe for circadian and metabolic pathway research. Its position in the published literature includes both the seminal characterization work (Solt et al. 2012) and subsequent published research identifying significant off-target activity and pharmacokinetic limitations (Dierickx et al. 2019). These published research findings make SR-9009 a useful but pharmacologically complex reference compound for laboratory studies of REV-ERB pharmacology, circadian biology, and nuclear receptor signaling.
| CAS Number | 1379686-30-2 |
| Other Names | SR9009, SR 9009, Stenabolic, X5DCA09N30, CHEMBL1961796, REV-ERB Agonist II, UNII-X5DCA09N30, GTPL8901 |
| IUPAC Name | ethyl 3-[[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]methyl]pyrrolidine-1-carboxylate |
| Molecular Formula | C₂₀H₂₄ClN₃O₄S |
| Molecular Weight | 437.9 |
| Dry-Fill Capsule Concentration | 15mg |
| Liquid Concentration And Solution | 30mg/ml (PEG400,DMSO) |
| Aliquot Concentration And Solution | 50mg/ml (MCT, Benzyl Benzoate, Benzyl Alcohol) |
