SLU-PP-332: What the Research Actually Shows
A synthetic small molecule that directly activates the same nuclear-receptor pathway exercise does, with real effects on body fat, glucose tolerance, and running endurance in mice, a newer orally active successor now in the literature, and, as of a 2025 study, the first evidence that it does something similar to living human muscle cells. Still zero completed human trials of any kind, and the compound itself isn't absorbed when taken by mouth. Here's exactly what two labs' worth of mouse data, one independent human-cell study, and two independent anti-doping laboratories' worth of attention actually show.
A Small Molecule That Flips On the Same Genetic Program Exercise Does
SLU-PP-332 is a synthetic small molecule, not a peptide, first developed by researchers at Saint Louis University, the source of its name, and carried forward by the same lead investigator, Thomas P. Burris, after his lab relocated to the University of Florida. It directly activates all three estrogen-related receptors, ERRα, ERRβ, and ERRγ, a family of nuclear receptors that, despite the name, have no established relationship to estrogen itself and are classified as orphan receptors because no naturally occurring hormone that activates them has been conclusively identified. ERRs sit immediately downstream of PGC-1α, the coactivator protein already well known as a master switch physical exercise uses to drive mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation, and Krebs cycle gene expression in muscle. Activating ERRs directly is, in effect, a way of triggering a meaningful piece of that same genetic program without a treadmill, which is why the compound has been described in the primary literature itself as an exercise mimetic. This guide treats that term as a description of mechanism, not a claim that an injection reproduces everything a real training program does for a person.
Evidence Summary
Mouse Mechanism Data, a First Look in Human Muscle Cells, and Two Anti-Doping Labs Paying Attention
Discovery: An ERRα-Dependent Boost to Exercise Capacity in Healthy Mice
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 Chemical Biology. 2023;18(4):756-771. doi: 10.1021/acschembio.2c00720. PMID: 36988910. This is the discovery paper. In normal-weight mice, SLU-PP-332 increased treadmill running duration by roughly 70% and distance covered by roughly 45% compared to untreated controls. The paper's title states the finding precisely: this acute exercise-capacity effect is ERRα-dependent, meaning it was shown to require a functional ERRα receptor rather than occurring through some unrelated pathway the compound happens to also activate. This is real, positive mouse data on a genuinely novel mechanism, in healthy animals rather than a disease model, and it's the foundation the rest of this compound's research program builds on.
Mouse Study (Healthy, Normal-Weight Animals) · Endpoint: Treadmill Running Duration and Distance, ERRα-Dependence Confirmed, Not a Human OutcomeA Second Mouse Model: Reversing Diet-Induced and Genetic Obesity
Billon C, Schoepke E, Avdagic A, Chatterjee A, Butler AA, Elgendy B, Walker JK, Burris TP. "A Synthetic ERR Agonist Alleviates Metabolic Syndrome." The Journal of Pharmacology and Experimental Therapeutics. 2024;388(2):232-240. doi: 10.1124/jpet.123.001733. In diet-induced obese mice given SLU-PP-332 (50 mg/kg, twice daily by injection, for 28 days) and separately in genetically obese ob/ob mice (12 days), treated animals lost roughly 12% body weight, gained roughly ten times less fat than untreated controls, and ran nearly 50% farther on a treadmill, all without any change in food intake, meaning the effect wasn't simply appetite suppression. The paper also reported improved glucose tolerance and insulin sensitivity in the treated animals. This is a second, independent mouse model, in diseased rather than healthy animals, converging on the same ERR-driven mechanism as the discovery paper above.
Mouse Study (Diet-Induced Obesity and Genetic ob/ob Obesity Models, 12-28 Days) · Endpoint: Body Weight, Fat Mass, Running Distance, Glucose Tolerance, and Insulin Sensitivity, Not a Human OutcomeThe First Human Cell Data: Restoring an "Active" Signature in Elderly Muscle Cells
Bonanni R, Falvino A, Matticari A, et al. "Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study." Frontiers in Physiology. 2025;16:1616693. doi: 10.3389/fphys.2025.1616693. This is the first SLU-PP-332 study to come from a research group with no connection to the Burris lab, and the first to use real human tissue. Researchers in Italy collected muscle biopsies during hip-replacement surgery from 20 elderly women, 10 who self-reported as physically active and 10 who reported being sedentary, and confirmed the biology behind the study's premise: the sedentary group's muscle showed smaller fiber diameter, weaker handgrip strength, more oxidative-stress markers, and lower levels of SIRT1, PGC-1α, ERRα, and FNDC5 (the exercise-induced myokine precursor) than the active group's. When muscle precursor cells (myoblasts) cultured from the sedentary donors were then treated with SLU-PP-332 in a dish for 48 hours, cell death fell, reactive oxygen species dropped by roughly 38%, the antioxidant glutathione rose by roughly 117%, markers of cellular senescence fell by roughly 26%, and SIRT1 and FNDC5 levels rose to match the untreated active donors' cells, with myotube formation comparable to the active group as well. This is not a person taking the drug, it's cultured cells from a small pilot study, but it's the first time SLU-PP-332's effect has been shown to hold in living human tissue rather than only in mice, and it lands on a genuinely relevant population: older, physically inactive adults, the group this compound's exercise-mimetic framing is most often proposed for.
Human Muscle Biopsies and Cultured Myoblasts, Independent Research Group (N=20 Donors) · Endpoint: Oxidative Stress, Senescence, and SIRT1/FNDC5 Restoration in Sedentary-Derived Cells, Ex Vivo, Not a Clinical TrialSolving the Oral-Delivery Problem: A Newer Analog, SLU-PP-915
Billon C, Appourchaux K, Côté I, Burris TP. "An orally active estrogen receptor–related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity." The Journal of Pharmacology and Experimental Therapeutics. 2026;393(1):103787. doi: 10.1016/j.jpet.2025.103787. (Published online December 2025.) SLU-PP-332 itself is not absorbed when given by mouth, every mouse result above used injection. This follow-up paper from the same lab introduces SLU-PP-915, a related pan-ERR agonist engineered specifically to be orally bioavailable. Given by mouth, SLU-PP-915 produced comparable efficacy to injected SLU-PP-332 once adjusted for how much of the drug actually reached circulation, and it robustly induced the same exercise-associated genes (including Ddit4) that treadmill running itself induces, in some cases matching or exceeding the levels produced by actual exercise. Combining SLU-PP-915 with an exercise-training program further boosted these gene-expression changes rather than simply substituting for training. This is still mouse-only data, but it directly addresses one of this compound family's most practical limitations, and it's a sign of continued, active development rather than a single finding that stalled.
Mouse Study, Oral Dosing · Endpoint: Oral Bioavailability, Exercise-Gene Induction, and Synergy With Exercise Training, Not a Human OutcomeTwo Independent Anti-Doping Laboratories Are Already Watching This Compound
Avliyakulov NK, Sobolevsky T, Ahrens E. "Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes." Drug Testing and Analysis. 2026;18(3):439-450. PMID: 41688415. Möller, Krug, Thevis. "In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential." Rapid Communications in Mass Spectrometry. 2026. PMID: 41588687. doi: 10.1002/rcm.70039. Two separate anti-doping laboratories, working independently of each other and of the Burris lab, published metabolite-identification studies on SLU-PP-332 (and, in the second paper, SLU-PP-915) within months of each other in early 2026, mapping nine metabolites of SLU-PP-332 and seven of SLU-PP-915 specifically so sports drug-testing programs can detect illicit use. Neither paper is a safety or efficacy study, both exist because anti-doping chemists judged this compound's exercise-mimetic mechanism plausible enough as a performance enhancer to build a detection method for it, ahead of any confirmed case of use in an athlete. As an unapproved compound not reviewed by any government regulatory health authority for human use, SLU-PP-332 falls under the same WADA S0 category, non-approved substances, already noted elsewhere in this Knowledge Center for other unapproved research compounds.
Analytical Chemistry / Doping-Control Studies, Two Independent Laboratories · Endpoint: Metabolite Identification for Detection Purposes, Not a Safety or Efficacy FindingWhat the Research Doesn't Yet Show
No human trial of any kind, safety, dosing, or efficacy, has been conducted or registered for SLU-PP-332 or SLU-PP-915. Every efficacy result described above comes from mice, and the one finding involving human tissue is a small pilot study of cultured cells, not a person who received the drug. Neither animal study ran longer than four weeks, so nothing here speaks to long-term safety in any species, let alone in a person. SLU-PP-332 itself is not orally bioavailable, so any product sold as an oral capsule or tablet cannot be delivering the compound the way it was actually studied, and its intended oral successor, SLU-PP-915, exists only in a single published mouse study so far. The mouse dosing used in these studies (50 mg/kg by injection, twice daily) does not translate directly to a human dose, and no published human pharmacokinetic data exists to make that conversion safely.
That two independent anti-doping laboratories have already built detection methods for this compound is itself part of the honest picture: it means people are very likely already using it outside of any clinical study, which is a reason for more caution, not less, given how little is actually known about human safety at any dose. Investigational research compound, not FDA-approved for any indication, not evaluated for human safety by any regulatory body.
How This Fits the Cellular Medicine Framework
SLU-PP-332 sits squarely at the mitochondrial-function and cellular-metabolism level of this framework. ERRα, ERRβ, and ERRγ are the direct downstream transcriptional partners of PGC-1α, the same master coactivator this framework already discusses in the context of exercise and metabolic health, and the genes they turn on together, mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, are the same machinery redox biology depends on to manage the electron transport chain's oxidative load. That connection isn't theoretical for this specific compound: the one human-cell study above measured a real drop in reactive oxygen species and a real rise in glutathione, the cell's primary antioxidant, right alongside the mitochondrial and senescence changes, which is why this guide treats the ERR pathway as a redox question as much as a mitochondrial one.
The pattern across the evidence above, a well-characterized mechanism, two independent mouse models pointing the same direction, a newer analog solving a real delivery problem, and now a first, genuinely encouraging signal in human cells from an unconnected research group, is exactly the kind of convergence this framework treats as a real reason to want the human trial that hasn't been run yet. It is not yet a reason to treat this compound as a proven answer for an individual patient today.
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. doi:10.1021/acschembio.2c00720 · PMID: 36988910
- Billon C, Schoepke E, Avdagic A, Chatterjee A, Butler AA, Elgendy B, Walker JK, Burris TP. A Synthetic ERR Agonist Alleviates Metabolic Syndrome. J Pharmacol Exp Ther. 2024;388(2):232-240. doi:10.1124/jpet.123.001733
- Bonanni R, Falvino A, Matticari A, Rinaldi AM, D'Arcangelo G, Cifelli P, Iundusi R, Gasbarra E, Tancredi V, Cariati I, Tarantino U. Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. Front Physiol. 2025;16:1616693. doi:10.3389/fphys.2025.1616693
- Billon C, Appourchaux K, Côté I, Burris TP. An orally active estrogen receptor–related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. J Pharmacol Exp Ther. 2026;393(1):103787. doi:10.1016/j.jpet.2025.103787
- Avliyakulov NK, Sobolevsky T, Ahrens E. Analysis and Identification of In Vitro Metabolites of Exercise Mimetic SLU-PP-332 ERRα/β/γ Agonist for Doping-Control Purposes. Drug Test Anal. 2026;18(3):439-450. PMID: 41688415
- Möller, Krug, Thevis. In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential. Rapid Commun Mass Spectrom. 2026. doi:10.1002/rcm.70039 · PMID: 41588687
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