SR-9009

SR-9009 (Stenabolic), also written SR9009 or SR 9009, is a synthetic small molecule that activates REV-ERBα and REV-ERBβ, nuclear receptors that repress core clock genes and link the circadian clock to metabolism. A team at The Scripps Research Institute in Florida reported it in 2012, with the sister compound SR-9011, as REV-ERB agonists with enough plasma and brain exposure for animal studies (Solt et al., 2012).

Published work on SR-9009 falls into six areas; each summary names its model. Apart from two case reports and anti-doping analyses, the evidence is from cell and animal studies, and one 2024 study in intervertebral disc cells was retracted in 2026 (Huang et al., 2024).

Discovery and circadian behavior in mice

In HEK293 reporter assays, SR-9009 increased REV-ERBα and REV-ERBβ repressor activity with IC50 values of 670 and 800 nM. In mice kept in constant darkness, one injection of SR-9009 or SR-9011 caused a loss of wheel-running activity in the next subjective night.

The agonists also altered daily clock gene expression in the hypothalamus and metabolic gene expression in liver, muscle and fat, and increased energy expenditure. In diet-induced obese mice, SR-9009 (100 mg/kg intraperitoneally, twice daily for 30 days) lowered fat mass, plasma triglycerides (12%), total cholesterol (47%), non-esterified fatty acids (23%) and glucose (19%) (Solt et al., 2012). Models: HEK293 cells and mice.

Skeletal muscle mitochondria

Mice lacking REV-ERBα had fewer muscle mitochondria, more autophagy and lower treadmill running capacity, while REV-ERBα overexpression raised mitochondrial number and respiration in muscle cells. Mice given SR-9009 (100 mg/kg intraperitoneally for 30 days) ran longer, in time and distance, than vehicle controls in a treadmill test to exhaustion, and SR-9009 or SR-9011 (5 µM) increased mitochondrial content in C2C12 muscle cells (Woldt et al., 2013). Models: mice, muscle fibers and C2C12 cells.

Sleep and anxiety-like behavior

In EEG recordings, SR-9011 (100 mg/kg intraperitoneally) given at mid-light phase, when REV-ERB expression peaks, increased wakefulness for about 2 hours and suppressed REM sleep for about 3; SR-9009 acted similarly, while SR-9011 given at mid-dark phase had no effect.

Given for 3 to 10 days, SR-9011 reduced anxiety-like behavior in open field, elevated plus maze, light-dark box and marble burying tests, SR-9009 was active in several of these assays, and SR-9011 had no effect in REV-ERBβ-null mice (Banerjee et al., 2014). SR-9009 also failed to raise wakefulness in REV-ERBβ-deficient mice (Amador et al., 2018). Models: wild-type and knockout mice.

Cancer cell lines and tumor models

SR-9009 and SR-9011 killed cancer cell lines from brain, leukemia, breast, colon and melanoma tumors, and oncogene-induced senescent cells, with little effect on the normal cells tested; the authors tied this to blocked autophagy and de novo lipogenesis, and REV-ERB knockdown abolished it.

In mouse glioblastoma models, including a patient-derived xenograft, SR-9009 slowed tumor growth and extended survival (Sulli et al., 2018). SR-9009 also inhibited prostate cancer cells and 22RV1 xenografts, but REV-ERB knockdown or knockout did not rescue the cells, and the authors traced the effect to LXRα (Xu et al., 2022). Models: cancer and senescent cells, and mouse xenografts.

Specificity and oral exposure

A University of Pennsylvania group built mice for conditional deletion of both REV-ERBs. In hepatocytes and embryonic stem cells lacking both receptors, SR-9009 still reduced cell viability, rewired metabolism and altered gene transcription, so its effects cannot be read solely as REV-ERB activity (Dierickx et al., 2019).

After oral gavage in mice, plasma SR-9009 stayed below 0.3 µg/mL while peak intestinal levels exceeded 10 µg/mL; the authors concluded that oral SR-9009 may act mainly in the gut, citing low systemic exposure and short half-lives (Yu et al., 2021). Most animal studies above used intraperitoneal injection. Models: knockout mouse cells and mice.

Doping control and case reports

An anti-doping laboratory found SR-9009 in a black-market product bought online, identified 8 metabolites of SR-9009 and 14 of SR-9011 in human liver microsomes, and found neither compound nor its metabolites in retrospective data from 1,511 doping-control samples (Geldof et al., 2016). An N-dealkylated metabolite in plasma and urine gave what the authors describe as the first adverse analytical finding for SR-9009 in equine doping control (Cutler et al., 2022).

Two case reports describe serious liver injury after use of products sold as SR-9009: acute liver failure needing an emergency transplant in a 17-year-old, with other causes excluded (Shams Bin Shaheen et al., 2026), and hepatocellular injury in a 40-year-old man after starting a product sold as Stenabolic (Govil et al., 2025). Neither report describes testing of the product. Models: liver microsomes, doping-control samples and two clinical cases.