SR9009 (Stenabolic) Research Guide | Rev-erb Agonism, Circadian & Metabolic Biology

What Is SR9009?

SR9009 (Stenabolic) is a synthetic Rev-erb α/β agonist developed at Scripps Research Institute by Thomas Burris. It activates both Rev-erbα and Rev-erbβ — nuclear receptors that are integral components of the mammalian circadian clock machinery and master regulators of metabolic gene programs.

SR9009 is not an androgen receptor agonist and should not be classified as a SARM in the mechanistic sense. It is grouped commercially with SARMs because of market conventions, but its research applications are primarily in circadian biology, metabolic disease, and inflammation — not in muscle/bone anabolism.

Rev-erb Biology

Rev-erbα and Rev-erbβ are nuclear receptors that:

Circadian clock: Act as negative regulators in the core circadian feedback loop, suppressing Bmal1 and Clock expression. The circadian clock drives ~10-15% of all mammalian gene expression — Rev-erb's position in this loop makes it a powerful transcriptional regulator
Lipid metabolism: Rev-erbα regulates triglyceride synthesis (SREBP-1c pathway), fatty acid oxidation, and bile acid metabolism in liver
Glucose metabolism: Gluconeogenesis regulation via HNF4α and PGC-1α — Rev-erb suppresses gluconeogenic gene expression
Inflammation: Rev-erbα suppresses NF-κB target genes in macrophages — anti-inflammatory via circadian/metabolic crosstalk

Published Research: Woldt et al. (2013)

The Woldt et al. (2013) paper in Nature Medicine is the landmark SR9009 metabolic study:

Fat mass: Diet-induced obese mice treated with SR9009 showed significant reduction in fat mass vs vehicle controls
Plasma lipids: Significant reduction in triglycerides, total cholesterol, and LDL
Insulin sensitivity: Improved glucose tolerance and insulin sensitivity in obese mouse models
Mitochondrial function: Increased mitochondrial number in skeletal muscle; improved oxidative capacity
Mechanism: Effects driven by Rev-erb-mediated gene program in liver, fat, and muscle; circadian regulation of metabolic gene expression

Important note on bioavailability: The Woldt study used IP injection in mice. SR9009's oral bioavailability is poor in rodents — a pharmacokinetic limitation that complicates in vivo oral dosing protocols. Researchers designing oral gavage studies should account for this.

Research Applications

Circadian biology: Rev-erb agonism is a standard molecular tool for circadian clock perturbation studies
Metabolic syndrome: Lipid and glucose metabolism effects in diet-induced obesity models
Atherosclerosis: Rev-erb regulation of macrophage inflammatory gene expression (NF-κB crosstalk)
Exercise mimetic comparison: SR9009 (Rev-erb), SLU-PP-332 (ERR), Cardarine (PPARδ), AICAR (AMPK) — distinct overlapping nodes of metabolic adaptation

Frequently Asked Questions

What is SR9009 (Stenabolic)?

SR9009 (Stenabolic) is a Rev-erb α/β agonist developed at Scripps Research Institute by the Burris laboratory. Despite being grouped with SARMs commercially, it does not bind the androgen receptor — it activates Rev-erb nuclear receptors, which are core components of the mammalian circadian clock and regulators of metabolic gene programs. Rev-erb agonism suppresses clock genes (Bmal1, Clock) and regulates lipid metabolism, glucose homeostasis, and inflammatory gene expression. It is prohibited in sport under WADA as a metabolic modulator. For Research Use Only.

What does SR9009 research show?

Published SR9009 research (Burris lab, Scripps): (1) Metabolic effects (Woldt et al., 2013, Nature Medicine): SR9009 in mice produced significant reduction in fat mass, improved insulin sensitivity, reduced plasma triglycerides and cholesterol, and improved mitochondrial function in skeletal muscle — all via Rev-erb agonism; (2) Circadian effects: SR9009 shifted circadian rhythms in cell culture and animal models; (3) Atherosclerosis: Rev-erb α/β regulate macrophage inflammatory gene expression — SR9009 showed anti-inflammatory effects in macrophage models relevant to atherosclerosis.