SR-9011 Overview
SR-9011 is a synthetic small-molecule ligand of the nuclear receptors REV-ERBα (NR1D1) and REV-ERBβ (NR1D2), and a close structural analog of SR-9009. Both compounds were originally developed at the Scripps Research Institute (Burris laboratory) and described in the 2012 Solt et al. Nature paper as tool compounds for investigating REV-ERB-mediated regulation of circadian rhythm, lipid and glucose metabolism, and mitochondrial gene expression.
In published in vitro reporter assays, SR-9011 has been characterized with IC₅₀ values of approximately 790 nM at REV-ERBα and 560 nM at REV-ERBβ, where it acts to increase the constitutive transcriptional repressor activity of the receptors. Published in vivo work has reported that SR-9011 achieves higher plasma concentrations and improved pharmacokinetics relative to SR-9009, making it the more commonly referenced of the two compounds in animal model research.
SR-9011 is not approved for human or veterinary use and is supplied strictly for laboratory and analytical research purposes.
Mechanism of Action (Research Context)
SR-9011 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 ≈ 790 nM at REV-ERBα; IC₅₀ ≈ 560 nM at REV-ERBβ in chimeric Gal4-LBD reporter systems
- Suppression of BMAL1 and CLOCK gene expression in REV-ERB-dependent cell models
- Improved in vivo bioavailability and brain exposure relative to SR-9009 in published rodent studies
- No activity reported across a panel of 46 other nuclear receptors in published selectivity profiling
- Modulation of circadian gene expression patterns in hypothalamus, liver, skeletal muscle, and adipose tissue in published rodent studies
Research Background: Off-Target Activity and Pharmacological Caveats
Subsequent published research has substantially refined the original characterization of the SR-9009 / SR-9011 chemical series as clean REV-ERB pharmacological probes. Dierickx et al. (2019, PNAS) reported that multiple effects originally attributed to REV-ERB engagement by SR-9009 and SR-9011 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 the utility of both SR-9011 and SR-9009 as selective REV-ERB tool compounds 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-9011 and reinforces the compound’s positioning as a research reagent rather than a definitive therapeutic or performance-related agent.
Chemical Structure & Identification
- Chemical Name: 3-[[(4-Chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]methyl]-N-pentylpyrrolidine-1-carboxamide
- Synonyms: SR-9011; SR9011
- Chemical Class: Synthetic nuclear receptor ligand — REV-ERBα/β agonist
- CAS Number: 1379686-29-9
- Molecular Formula: C₂₃H₃₁ClN₄O₃S
- Molecular Weight (average): 479.04 g/mol
- Exact Mass (monoisotopic): 478.181 g/mol
- PubChem CID: 71650463
Structural Description: SR-9011 shares the core scaffold of SR-9009 — a 1-pyrrolidine bearing a tertiary amine linker with a 4-chlorobenzyl arm and a 5-nitrothiophen-2-ylmethyl arm — but differs at the pyrrolidine nitrogen, where SR-9011 carries an N-pentyl carboxamide group (in contrast to SR-9009’s ethyl carbamate). This structural modification is associated with the compound’s improved in vivo bioavailability and brain exposure relative to SR-9009 in published preclinical PK studies. 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; 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-9011 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 alongside SR-9009 and across the broader REV-ERB ligand class (GSK4112, STL1267, and related compounds)
- Lipid metabolism, glucose handling, and mitochondrial gene expression signaling research
- Off-target pharmacology characterization (in light of published REV-ERB-independent activity)
- In vivo pharmacokinetic and ADME research, particularly in comparative studies with SR-9009
- Comparative metabolic-pathway research alongside PPAR-δ agonists (GW-501516, GW-0742) and related metabolic research compounds
Research Background & Regulatory Context
REV-ERB agonists, including SR-9011, are covered under the World Anti-Doping Agency (WADA) framework for metabolic modulators (S4.4 category). The U.S. Food and Drug Administration has issued public consumer advisories naming SR-class 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-9011 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-9011 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-9011 is a structurally defined synthetic REV-ERBα/β nuclear receptor ligand and close structural analog of SR-9009, with improved in vivo pharmacokinetics relative to SR-9009 in published preclinical studies. 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 (Dierickx et al. 2019). These published research findings make SR-9011 a useful but pharmacologically complex reference compound for laboratory studies of REV-ERB pharmacology, circadian biology, and nuclear receptor signaling.
| CAS Number | 1379686-29-9 |
| Other Names | SR9011, SR 9011, VYI79FLZ6W, CHEMBL1961797, UNII-VYI79FLZ6W, GTPL8900, DTXSID601045516, BDBM50366239, CS-4668, PPUYOYQTTWJTIU-UHFFFAOYSA-N |
| IUPAC Name | 3-[[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]methyl]-N-pentylpyrrolidine-1-carboxamide |
| Molecular Formula | C₂₃H₃₁ClN₄O₃S |
| Molecular Weight | 479.0 |
| Dry-Fill Capsule Concentration | 15mg |
| Liquid Concentration And Solution | 30mg/ml (PEG400, DMSO) |
| Aliquot Concentration And Solution | 50mg/ml (MCT, Benzyl Benzoate, Benzyl Alcohol) |
