Compound description
What is SR9009 powder (Stenabolic)
SR9009, also known as Stenabolic, is a synthetic agonist of the nuclear receptors REV-ERBα and REV-ERBβ. The compound was developed by Professor Thomas Burris at The Scripps Research Institute (Wikipedia). It is neither a hormone nor a SARM: SR9009 acts on an entirely different target — the transcriptional repressors at the core of the cell's molecular clock.
What REV-ERB is. These two receptors are key components of the circadian machinery. They repress expression of the genes that set the 24-hour rhythm while simultaneously governing metabolism: hepatic lipid and glucose handling, adipogenesis, and the inflammatory response of macrophages. SR9009 enhances this repressor activity with an IC₅₀ of 670 nM for REV-ERBα and 800 nM for REV-ERBβ (MedKoo). In effect the molecule provides pharmacological access to the biological clock.
Muscle and endurance. The most widely cited result came from Bart Staels' group: REV-ERBα proved to be highly expressed specifically in oxidative skeletal muscle, and its deficiency led to reduced mitochondrial content, diminished oxidative function and upregulated autophagy — mitochondria were both formed less readily and cleared more quickly. Pharmacological activation produced the opposite: increased mitochondrial density and improved exercise endurance. At the molecular level the Lkb1–Ampk–Sirt1–Ppargc-1α cascade is involved (Nature Medicine, 2013). It is this work that earned the compound its reputation as an "exercise mimetic".
Metabolism. In diet-induced obese mice, the REV-ERB agonist reduced body weight and improved the plasma lipid profile by raising energy expenditure. Notably, the effect was achieved without any change in food intake (review, Int J Mol Sci 2022). Animals on the agonists showed reduced fat mass and increased oxygen consumption.
Oncology — the most unexpected direction. A 2018 Nature paper showed that pharmacological activation of REV-ERB is lethal to cancer cells and to cells that have entered oncogene-induced senescence, while having no effect on the viability of normal cells and tissues (Nature, 2018). The mechanism involves regulation of autophagy and de novo lipogenesis: SR9009 reduces the number of autophagosomes, and in malignant cells this triggers apoptosis (ChemicalBook). The compound has become a lead structure for a new class of anticancer agents built around the circadian clock.
Heart and vasculature. SR9009 suppresses the development of atherosclerosis in a mouse model and substantially reduces pulmonary oedema, inflammatory cell infiltration and TNFα production in a rat model of ventilator-induced injury (ChemicalBook). In myocardial infarction models, short-term targeting of REV-ERBα produced long-term benefit for cardiac repair and inflammation reduction (review, Int J Mol Sci 2022).
Sleep and behaviour. Because the target sits at the core of the circadian machinery, SR9009 alters sleep architecture and emotional behaviour in animals, and reviews note benefits of REV-ERB agonists in jet lag and sleep disturbance (review, Int J Mol Sci 2022). The compound is regarded as a prototype for therapies addressing sleep disorders and metabolic disease.
Other models. Relief of osteoarthritis-associated pain has been demonstrated via reduced BMAL1 expression (ChemicalBook). In a mouse PCOS model, SR9009 improved follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy (Front Cell Dev Biol, 2021).
Supplied as a crystalline powder, purity ≥98% (Cayman Chemical), CAS 1379686-30-2.
