SR-9011 is a synthetic small molecule characterised in the published literature as an agonist at REV-ERBα and REV-ERBβ, molecular formula C23H31ClN4O3S, molecular weight 479.04. It is a small molecule rather than a peptide, developed as a chemical tool for probing nuclear receptor function.
Specification Table
SR-9011 verified chemical and handling data
| Property |
Value |
| Compound |
SR-9011 |
| Compound class |
Synthetic small molecule. Not a peptide |
| CAS number |
Contested. See note below |
| CAS, most widely cited |
1379686-29-9 |
| CAS, alternative in circulation |
1379686-30-2 |
| Molecular formula |
C23H31ClN4O3S |
| Molecular weight |
479.04 g/mol |
| Molecular targets |
REV-ERBα (NR1D1) and REV-ERBβ (NR1D2) |
| Reported IC50, REV-ERBα |
790 nM |
| Reported IC50, REV-ERBβ |
560 nM |
| Receptor superfamily |
Nuclear receptor |
| Endogenous receptor cofactor |
Heme |
| Transcriptional action of the receptor |
Repression, through NCoR and HDAC3 recruitment |
| Principal repressed target gene |
BMAL1 (ARNTL) |
| Originating group |
Burris and colleagues, Scripps Research Institute |
| Appearance |
Solid, typically white to off-white |
| Purity |
Per lot-specific certificate of analysis |
| Solubility |
Soluble in DMSO. Poorly soluble in water |
| Storage, solid |
-20°C, protected from light and moisture |
| Storage, DMSO stock |
-20°C or below, protected from moisture |
| Human clinical data |
None published |
| Regulatory status |
No approved human or veterinary formulation in any jurisdiction |
Which CAS Number Belongs to SR-9011?
Two registry numbers circulate for SR-9011 and they are not interchangeable. Anyone ordering, importing or documenting the material needs to know which one is correct.
1379686-29-9 is the number used by the major chemical suppliers, including Sigma-Aldrich, Cayman Chemical and MedChemExpress. It is the number that appears on most certificates of analysis and in most published methods sections.
1379686-30-2 appears in a smaller number of secondary sources. Registry numbers assigned in adjacent sequence frequently correspond to closely related entries, such as a free base and a salt form, or a compound and a stereoisomer, and a transcription error propagating through supplier listings is also common.
The practical guidance is to use 1379686-29-9 and to confirm against the certificate of analysis for the specific lot received. Where a shipping document or import declaration is involved, matching the number on the certificate rather than the number found online avoids an avoidable discrepancy.
This page states both numbers because concealing the ambiguity would be less useful than describing it. The same situation arises with MK-677 and with CJC-1295 elsewhere in this catalogue.
What Are REV-ERB Receptors?
REV-ERBα and REV-ERBβ, encoded by NR1D1 and NR1D2, are nuclear receptors with an unusual property that shapes everything about how they work.
Most nuclear receptors activate transcription when a ligand binds. REV-ERBs do the opposite. They lack the activation function-2 domain that other family members use to recruit coactivators, so ligand binding recruits the NCoR corepressor complex with HDAC3 instead, and transcription of target genes is repressed.
Their endogenous ligand is heme, which is itself notable. A nuclear receptor using heme as a cofactor links transcriptional regulation directly to cellular metabolic state, since heme availability reflects iron and porphyrin metabolism.
The principal target is BMAL1, a core component of the circadian transcriptional machinery. REV-ERB repression of BMAL1 forms one arm of the feedback loop that generates the roughly 24-hour oscillation in transcription found throughout mammalian tissues.
A synthetic agonist therefore acts as a chemical probe of that loop, which is what SR-9011 was developed for.
How Do the Reported Potency Values Read?
The published figures are IC50 values of 790 nM at REV-ERBα and 560 nM at REV-ERBβ, and reading them correctly requires noting what an IC50 means for a repressor.
For a receptor whose ligand-bound state represses transcription, a functional assay measures loss of reporter signal. The concentration producing half-maximal loss is reported as an IC50 even though the compound is acting as an agonist at the receptor. The nomenclature reflects the assay readout rather than the pharmacology.
Both values sit in the high nanomolar range, which is moderate potency. The roughly 1.4-fold difference between the two isoforms is small enough that SR-9011 should be treated as non-selective between them, and any design attributing an effect to one isoform specifically needs genetic rather than pharmacological separation.
Off-target activity deserves attention at the micromolar concentrations often used in cell work. A compound with a high-nanomolar on-target IC50 used at 10 micromolar is being applied more than tenfold above its characterised range, where selectivity claims weaken considerably.
Concentration-response covering the reported range rather than a single high concentration is the design that supports a mechanistic conclusion.
What Should SR-9011 Research Control For?
SR-9011 work carries specific methodological requirements that general pharmacology does not, and several of them are easy to omit.
Time of application matters. A compound acting on a circadian feedback loop produces different effects depending on the phase at which it is applied, and cultured cells retain circadian rhythms after synchronisation. Reporting the time of addition relative to a synchronising stimulus is necessary for the finding to be interpretable.
Synchronisation itself is a required step for most designs. Unsynchronised cultures contain cells at all phases, so a phase-dependent effect averages toward zero, and serum shock and dexamethasone pulses are the conventional methods.
A vehicle control matched for DMSO is essential given the poor aqueous solubility. DMSO has its own effects on cellular metabolism at concentrations above roughly 0.1 percent, and circadian gene expression is among the things it perturbs.
Genetic confirmation, through NR1D1 and NR1D2 knockdown or knockout, is the strongest available control. If an effect persists in cells lacking both receptors, it is not mediated by them regardless of what the compound was designed to do.
How Does SR-9011 Compare With Related Chemical Probes?
Several compounds target this receptor family and their differences determine which experimental questions each can answer.
SR-9009 is the closest relative, sharing the core scaffold and reported as a REV-ERB agonist with similar potency. The two are frequently used interchangeably, and published work has raised the question of whether some reported cellular effects of that compound occur independently of the receptor.
That question matters here by extension. Where two structurally related compounds produce the same effect, shared off-target activity is as plausible an explanation as shared on-target activity, and only genetic controls separate them.
SR-8278 is an antagonist at the same receptors and provides the pharmacological opposite arm. Where an agonist and an antagonist produce opposing effects on the same readout, receptor involvement is better supported than by either alone.
GSK4112 is an earlier tool compound in this area with poorer pharmacokinetic properties, useful mainly in cell-free and short cell-based work.
Running a matched pair, agonist and antagonist, alongside genetic manipulation is the design that supports a mechanistic conclusion. A single agonist at a single concentration supports considerably less than it appears to.
What Does Circadian Amplitude Measurement Involve?
Work on this receptor family usually needs oscillation measured rather than a single value, and that requires a different experimental setup than standard pharmacology.
Luciferase reporter systems driven by a clock gene promoter, most commonly PER2, allow continuous measurement from living cultures over several days. The output is a waveform rather than a number, and it carries three separable parameters.
Amplitude is the size of the oscillation. Period is its length. Phase is its position in time relative to the synchronising stimulus. A compound can alter any one without altering the others, and reporting only one obscures what happened.
Analysis requires detrending, since the raw signal declines as substrate depletes and cells age in culture, and that decline is not a change in the oscillation itself.
Damping rate is a fourth parameter worth extracting, describing how quickly the population oscillation decays. Damping can reflect either loss of rhythm in individual cells or loss of synchrony between cells that remain rhythmic, and single-cell imaging distinguishes them.
Reporting all four, with the analysis method stated, is what makes a circadian pharmacology finding comparable across laboratories.
What Should Be Recorded When Working With SR-9011?
Circadian pharmacology generates more variables than most cell work, and unrecorded ones make findings hard to compare.
Synchronisation method and time zero. Whether cells were serum-shocked or dexamethasone-pulsed changes the phase reference, and without a stated time zero a phase finding has no meaning.
Time of SR-9011 addition relative to that zero, in hours. A phase-dependent compound applied at an unstated time produces an uninterpretable number.
Final vehicle concentration, held identical across every condition. Dimethyl sulfoxide perturbs circadian gene expression at concentrations well within the range routinely used, which makes an unmatched vehicle a direct confound rather than a theoretical one.
Cell line and passage number, since circadian amplitude in cultured lines declines with passage and a low-amplitude culture will report a compound effect differently from a durablely rhythmic one.
Handling and Storage in Laboratory Practice
SR-9011 is handled as a small molecule, which means DMSO stocks rather than aqueous reconstitution.
Prepare a concentrated stock in anhydrous DMSO and store it in tightly sealed aliquots at -20°C or below. DMSO is hygroscopic and absorbs atmospheric water readily, and a stock that has taken up moisture may precipitate compound on freezing.
Allow aliquots to reach room temperature fully before opening, since condensation into cold DMSO is the usual route by which a stock becomes wet. Vortex briefly and inspect for precipitate before diluting into aqueous medium.
Dilute into medium slowly with mixing rather than adding medium to concentrated stock, which reduces local supersaturation and the precipitation it causes. Keep final DMSO concentration consistent across all conditions including controls.
Hold solid material at -20°C sealed against light and moisture. Record lot, the CAS number stated on the certificate, DMSO stock concentration, preparation date and final vehicle concentration in each condition.
Published Literature
References verified against the publisher record. The REV-ERB literature is substantially more independent than that for several compounds in this catalogue.
- Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, Burris TP. Nature. 2012;485(7396):62-68.
- Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA. Science. 2007;318(5857):1786-1789.
- Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U, Schibler U. Cell. 2002;110(2):251-260.
- Kojetin DJ, Burris TP. Nature Reviews Drug Discovery. 2014;13(3):197-216.
- Everett LJ, Lazar MA. Trends in Endocrinology and Metabolism. 2014;25(11):586-592.
Frequently Asked Questions
What is SR-9011?
A synthetic small molecule characterised as an agonist at the nuclear receptors REV-ERB alpha and beta, molecular formula C23H31ClN4O3S, molecular weight 479.04. It is a small molecule rather than a peptide, developed as a chemical tool. Laboratory research use only.
Which CAS number is correct?
Use 1379686-29-9. That is the number used by Sigma-Aldrich, Cayman Chemical and MedChemExpress, and it appears on most certificates of analysis. The alternative 1379686-30-2 circulates in a smaller number of secondary sources.
Why do two numbers circulate?
Registry numbers assigned in adjacent sequence often correspond to closely related entries, such as a free base and a salt form or a compound and a stereoisomer. A transcription error propagating through supplier listings is also a common explanation.
What are REV-ERB receptors?
Nuclear receptors encoded by NR1D1 and NR1D2 with an unusual property. They lack the activation function-2 domain other family members use to recruit coactivators, so ligand binding recruits the NCoR corepressor complex with HDAC3 and represses transcription instead.
What is the endogenous ligand?
Heme, which is notable in itself. A nuclear receptor using heme as a cofactor links transcriptional regulation directly to cellular metabolic state, since heme availability reflects iron and porphyrin metabolism rather than a dedicated signalling input.
What is the principal target gene?
BMAL1, a core component of the circadian transcriptional machinery. REV-ERB repression of BMAL1 forms one arm of the feedback loop generating the roughly 24-hour oscillation in transcription found across mammalian tissues.
Why is an agonist reported with an IC50?
Because the nomenclature reflects the assay readout rather than the pharmacology. For a receptor whose ligand-bound state represses transcription, a functional assay measures loss of reporter signal, and the half-maximal concentration is reported as an IC50.
Is SR-9011 selective between the isoforms?
No. The reported values of 790 and 560 nanomolar differ by roughly 1.4-fold, which is too small to support isoform selectivity, and any design attributing an effect to one isoform specifically needs genetic rather than pharmacological separation.
What does circadian work require methodologically?
Synchronisation before compound addition, since unsynchronised cultures contain cells at all phases and a phase-dependent effect averages toward zero. Serum shock and dexamethasone pulses are conventional, and time of application relative to that stimulus must also be reported.
What is the strongest available control?
Genetic confirmation through NR1D1 and NR1D2 knockdown or knockout. If an effect persists in cells lacking both receptors, it is not mediated by them regardless of what the compound was designed to target. A matched DMSO vehicle control is also essential.
Compliance Statement
SR-9011 is sold exclusively for laboratory research use. It is not a drug, food, or cosmetic product, and it is not a dietary product of any kind. It is not approved by the FDA or any comparable authority for human or veterinary use, it is a research chemical developed as a laboratory probe rather than a candidate for any other purpose, and no human study of it has been published. This product is not intended to diagnose, treat, cure, or prevent any disease. It must not be given to humans or animals. Purchase is restricted to qualified researchers and institutions operating within applicable laws. All handling is the responsibility of the purchasing laboratory.
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