SR-9011

SR-9011 is a synthetic agonist of the REV-ERB nuclear receptors, developed alongside and closely related in structure to SR-9009 in the Scripps program on circadian pharmacology ^[1]. Like its analogue, it enhances the repressive activity of REV-ERB-alpha and REV-ERB-beta, the clock-linked transcriptional repressors that coordinate rhythms of behavior and metabolism ^[1].

Its documented research applications are wide-ranging. The foundational report showed that synthetic REV-ERB agonists, including SR-9011, altered circadian behavior and the rhythmic expression of metabolic genes in liver, muscle, and fat, increasing energy expenditure and reducing obesity, dyslipidemia, and hyperglycemia in diet-induced obese mice ^[1]. Beyond metabolism, SR-9011 has been used to probe immunometabolism in microglia, where it disturbed clock gene rhythms and reduced phagocytosis and mitochondrial respiration ^[3]; oncology, where REV-ERB agonists were selectively lethal to cancer and senescent cells ^[2] and suppressed breast cancer cell proliferation ^[4]; and neuroscience, where REV-ERB agonists regulated sleep architecture and reduced anxiety-like behavior ^[5].

SR-9011 is an unapproved investigational research chemical with no clinical authorization, and its long-term metabolic effects in humans are unknown ^[1][3]. Like SR-9009 it is prohibited in sport, and analytical studies have characterized the metabolites of both compounds to support doping control ^[6]. It is typically supplied as a research-grade material. Its value is as a chemical probe for the intersection of the circadian clock with metabolism, inflammation, sleep, and cell growth, a set of connections it helped to reveal ^[1][2][5].

No human safety data at all. REV-ERB agonists broadly disrupt circadian and metabolic gene programs, which is inherently risky. Animal work shows sleep disruption. Treat as experimental with unknown long-term harms.

SR-9011 emerged from medicinal chemistry work at The Scripps Research Institute in Florida, in the laboratory of Thomas P. Burris, which was developing synthetic ligands to probe the REV-ERB nuclear receptors at the heart of the circadian clock. It was described in a foundational 2012 paper in Nature by Solt and colleagues alongside its close analogue SR-9009, where the two compounds were shown to alter circadian behavior and reprogram metabolism in mice. The stated purpose of the work was to create pharmacological tools that could target the body clock for the study and potential treatment of sleep and metabolic disorders. SR-9011 was never intended as a finished drug and has not undergone clinical development or human trials. It remains, together with SR-9009, a research chemical used to dissect how the circadian machinery connects to fuel metabolism, immunity, and cell proliferation.

SR-9011 holds a notable place in circadian biology as one of the first synthetic REV-ERB agonists potent enough to work in living animals, and it helped open an entire field exploring the clock as a druggable target. In rodent studies it is admired for reprogramming daily metabolism, raising energy expenditure, and reducing fat mass, results that have made it a frequent subject of interest among researchers and metabolism enthusiasts. Its value is best understood as that of a research tool: it has taught scientists a great deal about how timing genes govern the body's use of energy. Honesty requires noting that all of its documented effects come from cell and animal experiments, with no human data and a recognized potential to disrupt healthy circadian rhythms. For that reason it is regarded as a compelling scientific probe rather than an established supplement.