In 2023, headlines called it exercise in a pill. SLU-PP-332 is a small molecule that switches on the estrogen-related receptors, the same genetic switches muscle flips when it adapts to endurance training. In mice, it worked. In people, it has never been tested.
This guide explains what the estrogen-related receptors are, how SLU-PP-332 was found, what the two key mouse studies showed, why “exercise mimetic” oversells the result, and what is still unknown.
The short answer
- SLU-PP-332 is a synthetic small molecule, not a peptide, that activates all three estrogen-related receptors (ERRα, ERRβ and ERRγ), most potently ERRα. It came from Thomas Burris’s laboratory at Saint Louis University, the “SLU” in its name.
- Despite the name, estrogen-related receptors are not estrogen receptors and don’t respond to estrogen.
- In a 2023 mouse study, SLU-PP-332 increased oxidative type IIa muscle fibres and exercise endurance, an effect that depended on ERRα.
- In a 2024 study, obese mice given SLU-PP-332 burned more energy and fat, accumulated less fat mass and showed better insulin sensitivity.
- There are no human studies. SLU-PP-332 is not approved anywhere, and research-grade SLU-PP-332 is a laboratory reagent.
SLU-PP-332
Synthetic pan-ERR agonist. A small molecule, not a peptide.
- Formula
- C18H14N2O2, about 290.3 g/mol
- Targets
- ERRα, ERRβ and ERRγ; strongest at ERRα
- Developed
- Burris laboratory, Saint Louis University
- Key studies
- ACS Chemical Biology 2023; J Pharmacol Exp Ther 2024
- Status
- Not approved anywhere; no human studies
Where the evidence stands
- Cell studies
- Animal studies
- Human studies
- Controlled clinical trials
All published data come from cell experiments and mice.
What the estrogen-related receptors are
The estrogen-related receptors are three nuclear receptors, ERRα, ERRβ and ERRγ. The first were identified in 1988 by a team that included Vincent Giguère, who went on to lead ERR research at McGill University, and they were named for how closely their genes resemble the estrogen receptor’s. They don’t bind estrogen, and for years no natural activating molecule was known, which is why they are classed as orphan receptors.
Working with the coactivator PGC-1α, ERRα in particular switches on genes for building mitochondria, burning fatty acids and producing energy by oxidation. The receptors are most active in energy-hungry tissues such as the heart, skeletal muscle and brown fat, and endurance exercise raises their activity in muscle.
How SLU-PP-332 was found
Molecules that switch on ERRβ and ERRγ already existed, notably a compound called GSK4716, but ERRα had proved hard to target. Burris’s group used molecular modelling to redesign GSK4716, swapping one of its ring groups for a larger naphthalene ring. The new compound, SLU-PP-332, gained strong ERRα activity while keeping its activity at the other two receptors, and it was stable enough in the body to be used as a research tool in mice.
Research-grade SLU-PP-332 with a batch-matched COA.
View SLU-PP-332The 2023 endurance study
Published in ACS Chemical Biology, the first study started with muscle cells in culture, where SLU-PP-332 increased mitochondrial function and cellular respiration. In mice, it increased the share of type IIa fibres, the oxidative, fatigue-resistant fibre type that endurance training builds, and the treated mice ran longer before exhaustion.
The compound switched on an ERRα-driven gene program resembling the response to a bout of aerobic exercise, and ERRα activation proved critical for the endurance gain. Co-authors included Ronald Evans’s laboratory at the Salk Institute, a long-standing centre of nuclear receptor research.
The 2024 metabolic study
The follow-up, in the Journal of Pharmacology and Experimental Therapeutics, tested SLU-PP-332 in two mouse models of obesity: mice made obese on a high-fat diet and genetically obese ob/ob mice. Treated mice increased their energy expenditure and fatty-acid oxidation and accumulated less fat mass. The compound reduced obesity and improved insulin sensitivity in both models, effects the authors described as mimicking the whole-body metabolic benefits of exercise.
Why “exercise mimetic” oversells it
Exercise trains the heart, lungs, bones, blood vessels and brain as well as muscle metabolism. A compound that switches on one muscle gene program, even a central one, reproduces only a slice of that. The bigger caveat is that everything known so far comes from mice treated for a matter of weeks.
Earlier candidates show why caution matters. GW501516, a PPARδ agonist once promoted as exercise in a pill, was abandoned in development after it caused cancers in rodent studies. That doesn’t mean SLU-PP-332 shares that risk; it means the long-term studies that would reveal such risks haven’t been done.
What’s established and what isn’t
Reasonably well established
- SLU-PP-332 activates all three ERRs in cell assays, most strongly ERRα.
- In mice, it increased oxidative muscle fibres and endurance in an ERRα-dependent way.
- In obese mice, it reduced fat accumulation and improved insulin sensitivity.
Open questions
- Anything about effects or safety in people; no human studies exist.
- Effects on the heart, where ERRs are highly active.
- Long-term exposure, including ERRα’s role in the metabolism of some cancers.
- Whether any benefit persists after treatment stops.
Checking SLU-PP-332 on a COA
As a small molecule, SLU-PP-332 is simpler to verify than a peptide:
- Identity by mass spectrometry. Expect the protonated molecule at about m/z 291, matching a molecular weight of about 290.3 g/mol.
- Purity by HPLC, with the method and chromatogram shown. See our HPLC testing guide.
- Amount per unit. Formats that include fillers or excipients should report how much SLU-PP-332 each unit contains, not just its identity.
- A lot number matching what you receive. See our COA guide.
SLU-PP-332The pan-ERR agonistView product and COA
5-Amino-1MQSmall-molecule NNMT inhibitorView product and COA
MOTS-cExercise-linked mitochondrial peptideView product and COA
NAD+Coenzyme of energy metabolismView product and COA
Research use only. SLU-PP-332 from Pure Peptides Canada is a laboratory reagent for in-vitro research. It is not an approved drug or supplement, it is not for human or veterinary use, and nothing in this article is dosing or medical guidance.
Frequently asked questions
What is SLU-PP-332?
SLU-PP-332 is a synthetic small molecule that activates the estrogen-related receptors ERRα, ERRβ and ERRγ, most potently ERRα. It was developed in Thomas Burris’s laboratory at Saint Louis University and has been studied in mice.
Is SLU-PP-332 an estrogen?
No. Estrogen-related receptors were named for their structural resemblance to the estrogen receptor, but they don’t bind estrogen, and SLU-PP-332 is not a hormone or a steroid.
Why is SLU-PP-332 called an exercise mimetic?
In mice it switched on a gene program similar to the one muscle activates after aerobic exercise, increased oxidative muscle fibres and improved endurance. The label oversells it, because exercise affects far more than muscle metabolism.
What did the mouse studies show?
A 2023 study found greater exercise endurance and more oxidative type IIa muscle fibres, dependent on ERRα. A 2024 study in obese mice found higher energy expenditure and fat burning, less fat accumulation and better insulin sensitivity.
Has SLU-PP-332 been tested in humans?
No. All published data come from cell experiments and mice. Its safety and effects in people are unknown.
Is SLU-PP-332 a peptide?
No. It is a small organic molecule of about 290 g/mol. It is sold alongside research peptides because it is studied in related metabolic research.
Is SLU-PP-332 banned in sport?
It is not approved for human use anywhere, so it falls under the World Anti-Doping Agency’s S0 class of non-approved substances, which are prohibited at all times.
SLU-PP-332 for laboratory research
Research-grade SLU-PP-332 with an independent, batch-matched COA, tracked delivery across Canada and pricing in Canadian dollars.
References
- Billon C, Sitaula S, Banerjee S, et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(4):756–771. PMC
- Billon C, Schoepke E, Avdagic A, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024;388(2):232–240. DOI
- Giguère V, Yang N, Segui P, Evans RM. Identification of a new class of steroid hormone receptors. Nature. 1988;331(6151):91–94.
- World Anti-Doping Agency. The Prohibited List. WADA
For laboratory research use only. Not for human or veterinary use. This article summarizes published research for educational purposes and is not medical advice. Nothing here is intended to diagnose, treat, cure or prevent any disease.