SR-9009 (Stenabolic)
Rev-Erb Agonist | Circadian Rhythm & Metabolic Enhancement
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SR-9009 (Stenabolic) is a synthetic Rev-Erb agonist developed by Professor Thomas Burris at the Scripps Research Institute. Despite being almost universally marketed and sold alongside SARMs, SR-9009 is not a selective androgen receptor modulator and does not bind to or activate the androgen receptor in any capacity. Its mechanism is entirely distinct: it acts as an agonist of the Rev-Erb-alpha and Rev-Erb-beta nuclear receptors, which are key components of the molecular circadian clock and play critical roles in regulating lipid and glucose metabolism, inflammatory responses, and mitochondrial biogenesis. In preclinical studies conducted in mice, SR-9009 demonstrated notable effects on exercise capacity, metabolic rate, fat oxidation, and circadian rhythm regulation. Treated mice showed increased oxygen consumption, decreased fat mass, and enhanced endurance without changes in food intake. However, the most significant limitation of SR-9009 is its extremely poor oral bioavailability, estimated at approximately 2% in rodent models. This means that the vast majority of an orally administered dose is destroyed by first-pass hepatic metabolism before reaching systemic circulation. The impressive preclinical results were obtained via injection, raising serious questions about whether oral dosing in humans can achieve pharmacologically meaningful plasma concentrations. SR-9009 has never been tested in human clinical trials, is not approved for any medical use, and is classified as a prohibited substance by the World Anti-Doping Agency (WADA). It remains available through research chemical suppliers, where it is used in performance enhancement contexts primarily for its purported effects on fat loss, endurance, and energy levels.
SR-9009 functions as a synthetic agonist of the Rev-Erb-alpha (NR1D1) and Rev-Erb-beta (NR1D2) nuclear receptors. Rev-Erb proteins are constitutive transcriptional repressors that form a critical negative feedback loop within the mammalian circadian clock. They repress the transcription of BMAL1 and CLOCK, core clock genes that drive circadian oscillation of gene expression throughout the body. By activating Rev-Erb receptors, SR-9009 modulates circadian gene expression and thereby influences a broad array of downstream metabolic processes. In skeletal muscle, Rev-Erb activation by SR-9009 increases mitochondrial content and oxidative capacity. The compound upregulates genes involved in mitochondrial biogenesis, fatty acid oxidation, and glucose utilization. Studies in mice demonstrated that SR-9009 treatment increased the number of mitochondria in skeletal muscle, enhanced oxygen consumption, and improved exercise endurance. In the liver, Rev-Erb activation suppresses genes involved in lipogenesis (de novo fat synthesis) and gluconeogenesis, resulting in reduced hepatic fat accumulation and improved glucose homeostasis. In adipose tissue, SR-9009 reduces fat storage by downregulating genes involved in triglyceride synthesis. The net metabolic effect is an increase in energy expenditure and a shift toward a leaner metabolic phenotype. Critically, because SR-9009 acts through the Rev-Erb pathway and not the androgen receptor, it does not cause testosterone suppression, does not affect the hypothalamic-pituitary-gonadal axis, and does not require post-cycle therapy. The compound is entirely non-hormonal in its mechanism.
Molecular Data
Research Indications
SR-9009 increases basal metabolic rate and shifts fuel utilization toward fatty acid oxidation by enhancing mitochondrial activity. In mouse studies, treated animals showed reduced fat mass and body weight without changes in food intake. The compound suppresses lipogenesis in the liver and adipose tissue. However, the extremely poor oral bioavailability (~2%) raises significant questions about whether oral dosing achieves the plasma concentrations needed to replicate preclinical effects in humans.
Rev-Erb activation by SR-9009 increases mitochondrial content in skeletal muscle and enhances oxidative metabolism. In preclinical models, mice treated with SR-9009 (via injection) demonstrated meaningfully improved running endurance. Whether oral administration in humans can achieve sufficient bioavailability to reproduce these effects remains unestablished.
As a direct modulator of the molecular circadian clock, SR-9009 influences sleep-wake cycles and alertness. Rev-Erb activation promotes wakefulness and increases activity during normal waking periods. Users frequently report heightened alertness and energy, particularly when dosing in the morning and early afternoon. This effect may be a double-edged sword, as dosing too late in the day can cause insomnia.
Preclinical data support SR-9009's potential to improve multiple markers of metabolic syndrome, including reduced adiposity, improved glucose tolerance, and favorable lipid profiles. These findings have not been validated in human studies.
Rev-Erb agonism has demonstrated anti-inflammatory effects in preclinical models, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-alpha. SR-9009 reduced inflammation in mouse models of various conditions. Clinical translation has not been explored.
Dosing Protocols
SR-9009 is available in oral form as a liquid solution (typically in PEG-400 or similar carrier) or capsules from research chemical suppliers. The critical limitation of oral SR-9009 is its extremely poor oral bioavailability, estimated at approximately 2% in rodent pharmacokinetic studies. This means that ~98% of an oral dose is destroyed by first-pass hepatic metabolism before reaching systemic circulation. Combined with a short half-life of approximately 4 hours, oral SR-9009 requires multiple daily doses to attempt to maintain any meaningful plasma concentration. The preclinical studies demonstrating SR-9009's benefits used intraperitoneal injection, not oral administration. Whether oral dosing in humans can achieve pharmacologically relevant exposure remains a major open question and the primary criticism of SR-9009 as an oral supplement.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Research Dose - Standard | 20 mg/day (split: ~7 mg three times daily) | Three times daily, spaced 4-5 hours apart | Oral (liquid or capsule) |
| Research Dose - Upper Range | 30 mg/day (split: 10 mg three times daily) | Three times daily, spaced 4-5 hours apart | Oral (liquid or capsule) |
Interactions
What to Expect
Side Effects & Safety
Common Side Effects
- Insomnia or difficulty falling asleep if doses are taken too late in the day (the most frequently reported side effect)
- Increased wakefulness and alertness, which can be a benefit or drawback depending on timing
Stop Signs - Discontinue if:
- Severe or persistent insomnia that does not resolve with earlier dosing schedules
- Significant gastrointestinal distress
- Unexplained fatigue or malaise
- Signs of allergic reaction: rash, swelling, difficulty breathing
Contraindications
- Pre-existing sleep disorders or severe insomnia (Rev-Erb modulation may worsen these conditions)
- Pregnancy or potential pregnancy
- Breastfeeding
- Pre-existing liver disease (limited safety data and potential hepatic effects given Rev-Erb's role in liver metabolism)
- Individuals under 18 years of age
Quality Checklist
Good Signs
- Third-party lab tested with certificate of analysis (COA) showing purity above 98%
- Clearly labeled with compound name, concentration, batch number, and expiration date
- Solution is clear and free of particulate matter or discoloration
- Sold as a research chemical with appropriate disclaimers
- Supplier provides HPLC or mass spectrometry verification of identity and purity
Warning Signs
- No third-party testing or certificate of analysis available
- Marketed with explicit performance enhancement claims
- Labeled as a SARM (SR-9009 is not a SARM; this indicates supplier ignorance or mislabeling)
- Unusually low pricing compared to established suppliers
- Pre-made capsules without verifiable dosing accuracy
Bad Signs
- Cloudy, discolored, or precipitated solution indicating degradation or contamination
- No labeling, incorrect labeling, or missing batch/lot information
- Supplier has no verifiable reputation, reviews, or testing history
- Product tested by independent labs showing underdosed, mislabeled, or contaminated contents
- Contains unlisted active ingredients or adulterants
References
- Regulation of Circadian Behaviour and Metabolism by Synthetic REV-ERB AgonistsSolt, L.A., Wang, Y., Banerjee, S., et al.Nature (2012)
The landmark study introducing SR-9009 and SR-9011 as synthetic Rev-Erb agonists. Demonstrated that Rev-Erb activation by SR-9009 altered circadian gene expression, increased energy expenditure, reduced fat mass, and improved exercise endurance in mice. Treated animals showed increased oxygen consumption and decreased adiposity without changes in food intake. This paper established the pharmacological basis for SR-9009's metabolic effects.
- Rev-Erb-alpha Modulates Skeletal Muscle Oxidative Capacity by Regulating Mitochondrial Biogenesis and AutophagyWoldt, E., Sebti, Y., Solt, L.A., et al.Nature Medicine (2013)
Demonstrated that Rev-Erb-alpha is a key regulator of mitochondrial content and oxidative function in skeletal muscle. SR-9009 treatment increased mitochondrial number, enhanced oxidative capacity, and improved exercise endurance in mice. The study established the mechanistic link between Rev-Erb activation and mitochondrial biogenesis that underpins SR-9009's effects on exercise performance.
- Pharmacological Activation of REV-ERBs Is Lethal in Cancer and Oncogene-induced SenescenceSulli, G., Rommel, A., Wang, X., et al.Nature (2018)
Found that pharmacological activation of Rev-Erb receptors by SR-9009 and SR-9011 was selectively lethal to cancer cells and oncogene-induced senescent cells while having no effect on normal cell viability. This study suggested potential anti-cancer properties of Rev-Erb agonists, a notable contrast to the carcinogenicity concerns associated with the PPAR-delta agonist Cardarine.
- The Nuclear Receptor REV-ERBs: Bridging the Gap Between Circadian Rhythms, Inflammation, and MetabolismEverett, L.J., Lazar, M.A.Journal of Biological Chemistry (2014)
Comprehensive review of Rev-Erb biology covering the receptor's roles in circadian rhythm regulation, metabolic homeostasis, and inflammatory responses. Provided the mechanistic context for understanding how SR-9009's Rev-Erb agonism influences multiple physiological systems simultaneously, from lipid metabolism to immune function to sleep-wake regulation.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.