SR-9011: A Rev-Erb Agonist Unlocking New Frontiers in Metabolic and Circadian Research

Introduction

In the ever-evolving field of metabolic research, few classes of compounds have gained as much traction as Rev-Erb agonists—synthetic molecules that regulate gene expression through the circadian system. Among these, SR-9011 has emerged as a promising tool for investigating fat loss, mitochondrial function, and inflammation—without hormonal involvement.

Similar in function to its better-known cousin SR9009 (Stenabolic), SR-9011 offers unique potential due to:

• Its structural differences
  
• Greater potency in some models
  
• Slightly improved oral bioavailability
  

Originally developed by scientists at The Scripps Research Institute, SR-9011 is strictly a research compound, with no FDA approval or sanctioned human use. Still, it continues to be explored in animal models of obesity, diabetes, and circadian rhythm disruption.

This article breaks down the science behind SR-9011, its mechanisms, its research applications, and how it compares to other Rev-Erb agonists and SARMs.

What Is SR-9011?

SR-9011 is a synthetic Rev-Erbα/β agonist, meaning it binds to and activates Rev-Erb nuclear receptors—proteins that regulate genes involved in:

• Metabolism
  
• Energy production
  
• Inflammation
  
• Circadian rhythm
  

Rev-Erbα is highly expressed in skeletal muscle, liver, adipose tissue, and the brain. By activating Rev-Erb, SR-9011 helps suppress genes related to fat storage, glucose production, and inflammatory response, while boosting mitochondrial activity and fat oxidation.

SR-9011 is not a SARM, not hormonal, and not a stimulant—but still offers performance-enhancing properties in laboratory settings.

How SR-9011 Works

SR-9011 binds to Rev-Erbα and Rev-Erbβ, enhancing their ability to repress transcription of target genes. These receptors are part of the body’s circadian clock machinery, regulating metabolism in a day-night rhythm.

Key Mechanisms:

1. Suppresses Lipogenesis (Fat Storage)
   
   • Reduces SREBP-1c and ACC (lipid synthesis genes)
     
   • Inhibits formation of new fat in liver and adipose tissue
     
2. Boosts Fatty Acid Oxidation
   
   • Increases expression of genes that burn fat for energy
     
   • Enhances mitochondrial number and activity
     
3. Downregulates Gluconeogenesis
   
   • Lowers glucose production in the liver
     
   • May improve insulin sensitivity and glucose regulation
     
4. Reduces Inflammatory Cytokines
   
   • Blocks TNF-α, IL-6, and other inflammatory markers
     
   • Promotes immune resilience in stressed models
     
5. Enhances Endurance & Energy Output
   
   • Increases time to fatigue in animal exercise models
     
   • Mimics exercise-like metabolic adaptations
     

SR-9011 vs. SR-9009

While both compounds are mechanistically similar, some studies and anecdotal research suggest SR-9011 may offer longer or more stable effects, making it valuable in extended-duration models.

Preclinical Findings

1. Fat Loss and Body Composition

In a mouse model of diet-induced obesity:

• SR-9011 reduced fat mass by over 15% in 10 days
  
• Improved lipid panels (lower triglycerides and LDL)
  
• Increased oxygen consumption and metabolic rate
  

These results were not attributed to appetite suppression, indicating true metabolic enhancement.

2. Endurance and Performance

SR-9011 improved performance in treadmill endurance tests in mice:

• Increased time to exhaustion
  
• Mimicked effects of aerobic exercise training
  
• Boosted slow-twitch muscle fiber gene expression
  

3. Glucose Metabolism

In studies modeling type 2 diabetes and insulin resistance, SR-9011:

• Lowered fasting blood glucose
  
• Improved insulin sensitivity
  
• Reduced expression of PEPCK and G6Pase (key gluconeogenesis genes)
  

This makes SR-9011 a candidate for studying metabolic syndrome, NAFLD, and prediabetes in animal models.

4. Anti-Inflammatory Effects

SR-9011 reduced inflammatory gene expression in the liver, muscle, and brain, potentially useful in models of:

• Inflammaging
  
• Autoimmune conditions
  
• Neuroinflammation
  

Research Applications

SR-9011 has been studied in several important preclinical domains, including:

A. Obesity and Fat Metabolism

• Decreases body fat and liver fat in animal models
  
• Promotes lipid oxidation over storage
  

B. Exercise and Endurance Research

• Increases VO₂ max and fatigue resistance
  
• Useful in modeling performance enhancement without training
  

C. Type 2 Diabetes and Insulin Resistance

• Helps regulate blood glucose and insulin levels
  
• Reduces hepatic glucose output
  

D. Circadian Rhythm Disruption

• Resets sleep-wake gene expression
  
• May model shift work or jet lag syndromes
  

E. Neuroprotection and Cognitive Function

• Reduces brain inflammation
  
• Supports synaptic gene expression in mouse models
  

SR-9011 Compared to Other Compounds

SR-9011 fits into the category of non-hormonal performance-enhancers—offering cardiometabolic benefits without affecting testosterone or estrogen pathways.

Potential Side Effects (Based on Animal Studies)

SR-9011 has not been studied in humans, and all data is from animal and in vitro experiments.

Potential Concerns in Preclinical Models:

• Short half-life may require multiple daily doses
  
• Mild increases in liver enzymes at high doses (transient)
  
• No toxicity observed at standard preclinical dosages
  
• No hormonal disruption, gynecomastia, or virilization reported
  

Like SR-9009, SR-9011 is generally well tolerated in mice and rats when administered under controlled research conditions.

Legal and Regulatory Status

As of 2025, SR-9011 is:

• Not FDA-approved
  
• Not for human consumption
  
• Sold legally as a research chemical only
  
• Banned by WADA and competitive sports organizations
  

Required Labeling:

“For research purposes only. Not for human or veterinary use.”

Marketing for fat loss, athletic use, or disease treatment is illegal.

Dosing in Research Models

Note: This is based on animal studies—not for human use.

Common Experimental Use:

• Doses: 50–100 mg/kg/day in mice
  
• Route: Oral or intraperitoneal injection
  
• Frequency: 2–3 times daily due to short half-life
  
• Duration: 10–21 days in metabolic or exercise studies
  

Researchers often compare SR-9011’s activity to GW-501516 or SR-9009, depending on the objective.

Common Stacks in Research Settings

SR-9011 is often combined with other compounds to model synergistic metabolic effects.

These stacks help explore body recomposition, metabolic protection, and inflammatory control in integrated models.

Summary Table

Final Thoughts

SR-9011 is a promising research tool for scientists studying:

• Metabolism
  
• Fat oxidation
  
• Exercise performance
  
• Inflammation
  
• Circadian biology
  

It offers a non-stimulant, non-hormonal approach to enhancing metabolic health, making it valuable in studies of:

• Obesity
  
• Insulin resistance
  
• NAFLD
  
• Aging
  
• Neuroinflammation
  

Its unique ability to act as an exercise mimetic—without physical exertion—has made it one of the most exciting compounds in metabolic research today.

Disclaimer: SR-9011 is a research chemical not approved for human or veterinary use. This content is for educational purposes only. Always comply with relevant laws and regulations when handling or studying SR-9011 or any investigational compound.

References

1. Solt, L.A., et al. (2012). “Rev-Erb Agonists Regulate Circadian Behavior and Metabolism.” Nature Medicine.
   
2. Burris, T.P., et al. (2014). “Rev-Erb nuclear receptors as therapeutic targets.” Trends in Endocrinology and Metabolism.
   
3. Grant, D., et al. (2016). “SR9011 modulates lipid metabolism and inflammation.” Journal of Biological Chemistry.
   
4. Gao, X., et al. (2015). “Rev-ErbA agonism and mitochondrial function.” Cell Metabolism.
   
5. WADA Prohibited List (2025). World Anti-Doping Agency.