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Overview
What is SLU-PP-332?
SLU-PP-332 is a groundbreaking synthetic small-molecule compound developed at Saint Louis University that functions as a pan-estrogen-related receptor (ERR) agonist with preferential activity at ERRα. Often called an 'exercise mimetic,' it activates metabolic pathways typically engaged during physical exercise without requiring actual physical activity. By enhancing mitochondrial biogenesis, fatty acid oxidation, and energy expenditure, SLU-PP-332 has demonstrated remarkable effects across multiple systems including weight loss (12% in 28 days), improved exercise capacity (70% increase in endurance), enhanced insulin sensitivity, cardiac protection, and reversal of age-related mitochondrial dysfunction. While showing tremendous promise in preclinical studies with favorable safety profiles in multiple animal models, it remains in research-only status with no human clinical trials yet conducted. Researchers at the University of Florida are working to advance this compound toward human studies and developing an oral pill formulation for easier administration.
Key Benefits
Exercise mimetic effects without physical activity, significant weight loss (12% in 28 days), 70% increased endurance, 25% enhanced fatty acid oxidation, improved insulin sensitivity, reduced hepatic steatosis, cardiac protection, reversal of age-related mitochondrial dysfunction, enhanced muscle oxidative capacity
Mechanism of Action
Binds to and activates estrogen-related receptors (ERRα, ERRβ, ERRγ) which regulate gene expression for energy metabolism. Upregulates PGC-1α (master regulator of mitochondrial biogenesis), activates AMPK pathway (cellular energy switch), increases mitochondrial density up to 1.8-fold, enhances oxidative phosphorylation and ATP production, promotes fatty acid oxidation, induces type IIa oxidative muscle fiber genes, and activates acute aerobic exercise genetic programs.
Molecular Information
Weight
290.32 Da
Length
Non-peptide small molecule
Type
Synthetic ERR agonist
Amino Acid Sequence:
Not applicable - synthetic small molecule
* (E)-4-Hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide. Chemical formula: C₁₈H₁₄N₂O₂. Pan-ERR agonist with 2.3-fold selectivity for ERRα (EC50 = 98 nM) over ERRβ (230 nM) and 4.4-fold selectivity over ERRγ (430 nM).
Research Indications
Weight Loss & Body Composition
Preclinical studies show 12% body weight reduction in 28 days without appetite suppression or increased activity. Fat mass gain <0.5g vs ~5g in controls. Decreases white adipocyte size and shifts metabolism toward lipid utilization.
Insulin Sensitivity & Glucose Control
Significantly improved glucose tolerance in obese mice with lower fasting glucose and insulin levels. Enhanced insulin sensitivity comparable to first-line diabetes medications through increased glucose uptake and fatty acid oxidation.
Energy Expenditure Enhancement
Increases resting energy expenditure by 25% for fatty acid oxidation. Shifts fuel utilization toward lipids (decreased respiratory exchange ratio within 2 hours) without acting as a stimulant.
Liver Health & NAFLD
Reduced hepatic steatosis (fatty liver), decreased hepatic triglycerides, and enhanced hepatic fatty acid oxidation. Potential therapeutic applications for non-alcoholic fatty liver disease.
Research Protocols
Disclaimer
These are commonly discussed research protocols and not medical advice. Consult a healthcare provider before use.
Timing
Animal studies used IP injection twice daily. Human administration protocols DO NOT EXIST. Researchers are developing oral pill formulation for potential future human use pending clinical trials.
Peptide Interactions
How to Reconstitute
Important
SLU-PP-332 is insoluble in water - use DMSO instead of bacteriostatic water. Dissolve in pure DMSO first (50-125 mg/mL), then dilute with carriers for in vivo use.
This is a lipophilic small molecule, not a peptide - it will NOT dissolve in water-based solutions
Dissolve SLU-PP-332 in pure anhydrous DMSO first to create a stock solution (up to 50-125 mg/mL)
For in vivo use, dilute DMSO stock with carriers: 10% DMSO + 10% Tween 80 + 80% PBS (from published studies)
Alternative formulation: 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline
Oil-based alternative: 10% DMSO + 90% corn oil
Ensure solution is completely clear before adding each solvent - use vortex, ultrasound, or gentle warming
Final DMSO concentration should not exceed 10% for in vivo applications
Store DMSO stock solutions at -80°C (6 months) or -20°C (1 month) - avoid repeated freeze-thaw
Quality Indicators
Insoluble in water - use DMSO
SLU-PP-332 is a lipophilic small molecule that will not dissolve in water. Use DMSO as the primary solvent (50-125 mg/mL), not bacteriostatic water.
Research Chemical Only - NOT FOR HUMAN USE
SLU-PP-332 is NOT FDA approved and has NOT been tested in human clinical trials. It is legally available only for legitimate research purposes through licensed suppliers.
Products Marketed for Human Consumption
Any SLU-PP-332 marketed, sold, or labeled for human consumption is illegal and potentially dangerous. Suppliers should clearly label as 'For Research Use Only' with proper regulatory disclaimers.
Unknown Purity or Contamination
Without proper laboratory testing (HPLC, mass spectrometry), purity and identity cannot be verified. Contaminated or misidentified compounds pose serious health risks.
No Quality Control Standards Exist
Since SLU-PP-332 is not approved for human use, there are no GMP (Good Manufacturing Practice) standards or USP monographs. Quality varies widely between suppliers.
Legitimate Research Supplier
If obtained for legitimate research, should come from reputable chemical suppliers (Cayman Chemical, Sigma-Aldrich, etc.) with Certificate of Analysis, proper labeling, batch numbers, and purity data (typically >98%).
What to Expect
- •Metabolic shift toward fat oxidation (decreased respiratory exchange ratio within 2 hours)
- •Gene expression changes detectable at 3-6 hours
- •Measurable plasma (0.2 μM) and muscle (0.6 μM) concentrations at 6 hours
- •Enhanced exercise performance in acute dosing studies (1 hour post-dose)
- •Increased resting energy expenditure becomes measurable
- •Enhanced fatty acid oxidation (25% increase)
- •Initial metabolic adaptations and mitochondrial remodeling begins
- •Improved grip strength becomes observable by day 6
- •Significant weight loss (up to 12% by day 28 in animal studies)
- •Fat mass reduction dramatically different from controls (<0.5g vs ~5g gain)
- •Improved glucose tolerance and insulin sensitivity
- •Enhanced exercise endurance (45-70% improvements in running performance)
- •Muscle fiber type changes toward oxidative phenotype
- •Reduced hepatic steatosis becomes evident
- •Cardiac improvements evident (improved ejection fraction, reduced fibrosis)
- •Structural cardiac and muscle remodeling continues
- •Reversal of age-related kidney dysfunction (if applicable)
- •Restoration of mitochondrial architecture in multiple tissues
- •Reduced inflammatory and senescence markers in aging tissues
- •Sustained anti-aging effects observed in preclinical aging studies
- •Continued improvement in tissue mitochondrial function
- •Reversal of cellular senescence markers maintained
- •Duration of effects after discontinuation is UNKNOWN in humans
- •Whether tolerance develops with chronic use remains UNSTUDIED
Side Effects & Safety
- NOT FDA APPROVED - FOR RESEARCH USE ONLY
- Animal studies show favorable safety profile with no severe side effects at therapeutic doses
- Well-tolerated in rodents and canines with no liver, kidney, or cardiac toxicity
- No adverse effects on pancreatic histology, lean mass, or body temperature regulation
- Does not suppress hormones or act as a stimulant in animal models
- Minor changes in plasma cholesterol and liver enzymes noted in some studies
- High doses or prolonged exposure may have uncharacterized side effects
- Potential effects on insulin sensitivity - may interact with diabetes medications
- Human safety profile is COMPLETELY UNKNOWN - extrapolation from animals is unreliable
- Legal status varies by jurisdiction - may be restricted or illegal in many areas
- NEVER use experimental compounds without medical supervision and regulatory approval
References
A Synthetic ERR Agonist Alleviates Metabolic Syndrome - 2024
Landmark study demonstrating 12% body weight loss, 25% increase in fatty acid oxidation, improved glucose tolerance, and reduced hepatic steatosis. Fat mass gain was <0.5g vs ~5g in controls. No adverse pancreatic effects observed. Published in Journal of Pharmacology and Experimental Therapeutics.
View Study (opens in new tab) →Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction in Aging Kidney - 2023
Groundbreaking aging study showing reversal of age-related kidney decline. Reduced albuminuria, prevented podocyte loss, restored mitochondrial architecture via electron microscopy, decreased inflammatory cytokines and senescence markers. First compound to directly improve mitochondrial health in aging. Published in American Journal of Pathology.
View Study (opens in new tab) →Synthetic ERRα/β/γ Agonist Induces Acute Aerobic Exercise Response - 2023
First demonstration that pharmacological ERR activation replicates acute exercise genetic programs. Showed 70% increase in running time, 45% increase in distance, increased type IIa oxidative muscle fibers, and progressive grip strength improvements. ERRα confirmed as critical isoform via knockout studies. Published in ACS Chemical Biology.
View Study (opens in new tab) →Quick Start Guide
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