SR9009 (Stenabolic): A REV-ERB Agonist, Not a SARM

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For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.

SR9009, sold under the name Stenabolic, is another compound that research catalogs commonly list alongside SARMs even though it has nothing to do with the androgen receptor. SR9009 is a synthetic agonist of REV-ERB-alpha and REV-ERB-beta, nuclear receptors that sit at the center of the molecular circadian clock and link daily rhythms to metabolism.

It is one of the most cited circadian tool compounds of the past decade, and its literature includes an important twist: later genetic work showed that some of its effects occur even when REV-ERB is absent. This review covers the mechanism, research history, key findings and practical considerations. Explicit SARMs supplies SR 9009 Stenabolic Capsules strictly as laboratory reference material.

What Is SR9009?

  • Common names: SR9009, SR-9009, Stenabolic
  • Class: synthetic REV-ERB-alpha/beta agonist (not a selective androgen receptor modulator)
  • Primary targets: REV-ERB-alpha (NR1D1) and REV-ERB-beta (NR1D2)
  • Originator: The Scripps Research Institute (Burris laboratory)
  • Related compound: SR9011
  • Research setting: cell and rodent studies; no human clinical trials
  • Regulatory status: not approved by the FDA or any other regulator for any indication

Mechanism of Action

The mammalian circadian clock runs on a transcriptional feedback loop. The activators CLOCK and BMAL1 drive expression of their own repressors, including the PER and CRY proteins and the REV-ERB receptors. REV-ERB-alpha and REV-ERB-beta are transcriptional repressors: when active, they recruit the corepressor NCoR and histone deacetylase 3 to target genes, including BMAL1 itself. Their natural ligand is heme.

SR9009 was designed to enhance REV-ERB repressive activity. In the foundational 2012 Nature study, Solt and colleagues reported that synthetic REV-ERB agonists altered circadian behavior and the rhythm of core clock gene expression in the mouse hypothalamus, and changed the daily expression patterns of metabolic genes in liver, skeletal muscle and adipose tissue, with increased energy expenditure. [1]

Because REV-ERB activity affects lipid metabolism, glucose handling, inflammation and mitochondrial function, SR9009 became a widely used tool for probing how the clock regulates metabolism.

Research History

SR9009 and SR9011 were developed at The Scripps Research Institute and described in 2012. [1] Over the following years, they were used in studies of skeletal muscle oxidative capacity [2], sleep and wakefulness, inflammation, and cancer cell biology. [3]

In 2019, a study from the University of Pennsylvania used mice in which both REV-ERB-alpha and REV-ERB-beta could be genetically deleted. The authors found that SR9009 still reduced cell viability, rewired cellular metabolism and altered gene transcription in hepatocytes and embryonic stem cells lacking both receptors. They concluded that the effects of SR9009 “cannot be used solely as surrogate for REV-ERB activity.” [4] That finding reshaped how the compound’s literature should be read.

What Published Studies Report

Circadian and metabolic studies in mice

In the 2012 study, treatment of diet-induced obese mice with a REV-ERB agonist reduced fat mass and improved dyslipidemia and hyperglycemia. [1] In those mouse experiments the compound was administered by injection, which is worth noting when comparing study designs.

Skeletal muscle

Woldt and colleagues reported in 2013 that REV-ERB-alpha is highly expressed in oxidative skeletal muscle and that its deficiency reduced mitochondrial content and oxidative function. Pharmacological activation of REV-ERB-alpha in mice increased exercise capacity in that model. [2]

Cancer cell biology

A 2018 Nature study reported that SR9009 and SR9011 were lethal to several cancer cell types and to oncogene-induced senescent cells, while sparing normal cells in the systems tested, through effects on autophagy and de novo lipogenesis. In a mouse glioblastoma model, they impaired tumor growth. [3] Given the later REV-ERB-independent findings [4], how much of this activity runs through REV-ERB remains an open question.

Metabolism and detection

Geldof and colleagues characterized SR9009 and SR9011 metabolites in human liver microsome assays, identifying eight metabolites of SR9009, and confirmed SR9009 in a product purchased online. [5] This work supports analytical method development.

Research Considerations

  • On-target controls. Because SR9009 has documented REV-ERB-independent effects, include REV-ERB knockout or knockdown controls before attributing results to REV-ERB. [4]
  • Time of day matters. REV-ERB activity follows the circadian cycle, so the timing of administration and tissue collection should be standardized and reported in zeitgeber time.
  • Route and exposure. Foundational mouse work used injection. Measure plasma exposure rather than assuming it, especially for other routes.
  • Comparator compounds. SR9011 and other REV-ERB ligands help distinguish class effects from compound-specific effects.
  • Correct classification. SR9009 is not a SARM. Androgen-receptor endpoints are not relevant to its mechanism.

SR9009 Versus True SARMs

SR9009 is grouped with SARMs in many catalogs, but the two classes have almost nothing in common pharmacologically:

  • Target. SARMs bind the androgen receptor. SR9009 targets REV-ERB-alpha and REV-ERB-beta, which are transcriptional repressors in the circadian clock.
  • Mode of action. Androgen receptor agonists activate gene transcription. REV-ERB agonists enhance gene repression.
  • Time dependence. SARM activity is not strongly tied to time of day, while REV-ERB activity follows the circadian cycle.
  • Evidence base. Several SARMs have human trial data. SR9009 has none and is studied only in cells and animals.
  • WADA section. SR9009 falls under S4.4 Metabolic Modulators, not S1.2. [6]

A REV-ERB study design should therefore look very different from a SARM study design, with standardized circadian timing, clock gene readouts and genetic controls as the core features.

Interpreting the Older Literature

The 2019 REV-ERB-independence finding does not invalidate earlier SR9009 research, but it changes how conclusions should be drawn. [4] Effects observed with SR9009 alone show what the compound does in a given model, not necessarily what REV-ERB activation does. Papers that combined SR9009 with genetic deletion of REV-ERB carry more weight on mechanism than papers that relied on the compound alone.

WADA Status

SR9009 is prohibited at all times under WADA section S4.4 (Metabolic Modulators). [6]

Storage, Purity and COA

  • Store capsules sealed, dry and away from light and heat.
  • Log lot numbers and receipt dates in study records.
  • Review the lot-specific Certificate of Analysis, which should report HPLC purity, confirm identity by mass spectrometry, and list the lot number and test date.

For lot documentation, use the contact page.

Related Research Compounds

Frequently Asked Questions

Is SR9009 a SARM?

No. SR9009 is a REV-ERB agonist. It does not bind the androgen receptor and is grouped with SARMs by market convention only.

What does REV-ERB do?

REV-ERB-alpha and REV-ERB-beta are nuclear receptors that repress core clock genes such as BMAL1 and help coordinate daily rhythms of metabolism in the liver, muscle and fat.

Are all SR9009 effects caused by REV-ERB?

No. A 2019 study showed that SR9009 affected cell viability, metabolism and gene expression in cells lacking both REV-ERB receptors. [4]

Has SR9009 been tested in humans?

No. There are no registered or published human clinical trials of SR9009.

Is SR9009 approved by the FDA?

No. SR9009 has never been approved by the FDA or any other regulator.

Is SR9009 prohibited in sport?

Yes. It is prohibited at all times under WADA section S4.4. [6]

What is the difference between SR9009 and SR9011?

Both are synthetic REV-ERB agonists from the same Scripps program and were described together. They are structurally related, and studies often use both to check whether an effect is shared across the chemical series. [1][3][5]

Why is time of day important in SR9009 studies?

REV-ERB expression and activity rise and fall over the circadian cycle, so the same exposure at different times can produce different results. Standardizing and reporting timing is essential. [1]

References

  1. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012. PubMed 22460951
  2. Woldt E, et al. Rev-erb-alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy. Nat Med. 2013. PubMed 23852339
  3. Sulli G, et al. Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence. Nature. 2018. PubMed 29320480
  4. Dierickx P, et al. SR9009 has REV-ERB-independent effects on cell proliferation and metabolism. Proc Natl Acad Sci U S A. 2019. PubMed 31127047
  5. Geldof L, et al. In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011. Int J Mol Sci. 2016. PubMed 27706103
  6. World Anti-Doping Agency. 2026 Prohibited List. wada-ama.org

For laboratory research use only. Not for human consumption. All compounds referenced in this article are sold by Explicit SARMs solely as reference materials for in-vitro and animal research by qualified professionals. Nothing here is medical advice, and no statement has been evaluated by the FDA. These materials are not intended to diagnose, treat, cure or prevent any disease.

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