SLU-PP-332 is a laboratory research chemical that activates the estrogen-related receptors (ERRα, ERRβ and ERRγ), a family of proteins that help control how muscle and heart cells build mitochondria and burn fat. Academic groups developed it as a chemical probe, and the papers describing it call it an “exercise mimetic” because in mice it switches on part of the gene program that aerobic exercise normally triggers.
The most important fact about it is how little is known: SLU-PP-332 has never been tested in humans. Everything below comes from mice, rat heart cells, or cells in culture. It is not an approved medicine in any country, and a search of ClinicalTrials.gov returns no registered studies of it (ClinicalTrials.gov). Its safety profile in people, including how it is cleared, what organs it affects and what doses would do anything, is simply unknown.
This page summarizes what the published preclinical literature reports. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Synthetic pan-ERR agonist (ERRα, ERRβ, ERRγ); preclinical chemical probe |
| Chemistry | C₁₈H₁₄N₂O₂; molecular weight 290.3 g/mol; PubChem CID 5338394 |
| Potency in cell reporter assays | ERRα EC50 98 nM; ERRβ 230 nM; ERRγ 430 nM |
| Approval status | None. Not approved by FDA, EMA or any other regulator; no human trials published |
| Evidence base | Mouse and cell studies only (exercise capacity, obesity, heart failure, aging kidney) |
| Human half-life | Not established. Human liver microsome half-life in vitro 31.3 min |
| Oral activity | Poor; the developers state it “lacks oral bioavailability” and used injection in mice |
| WADA status | Prohibited at all times under S0 (non-approved substances) |
| US controlled substance | Not scheduled under 21 CFR 1308.13 |
What it is
SLU-PP-332 is 4-hydroxy-N’-(naphthalen-2-ylmethylene)benzohydrazide, an acyl hydrazone with the formula C₁₈H₁₄N₂O₂ and a molecular weight of 290.3 g/mol (PubChem CID 5338394). It is not a steroid, not a SARM and not a peptide. It is a small synthetic molecule that binds a nuclear receptor unrelated to the androgen receptor.
The estrogen-related receptors are “orphan” nuclear receptors: they are constitutively active, and no natural hormone that switches them on has been identified. Despite the name, they are not activated by estrogens. They are most abundant in high-energy tissues such as skeletal muscle, heart and liver, where their target genes encode proteins for fatty acid oxidation, mitochondrial biogenesis and the Krebs cycle (Billon et al., J Pharmacol Exp Ther 2024).
A group at Saint Louis University started from GSK4716, an ERRβ/γ-selective agonist, and optimized it for activity at ERRα, which had been the hardest of the three to target. The result, reported in 2023, was SLU-PP-332, with roughly 50-fold more ERRα potency than the starting compound (Billon et al., ACS Chem Biol 2023):
| Receptor | SLU-PP-332 EC50 | GSK4716 EC50 |
|---|---|---|
| ERRα | 98 nM | over 5,000 nM |
| ERRβ | 230 nM | over 5,000 nM |
| ERRγ | 430 nM | 1,200 nM |
Full-length receptor cotransfection assays. SLU-PP-332 is 4.4-fold selective for ERRα over ERRγ and 2.3-fold over ERRβ.
In the same paper, SLU-PP-332 did not change the activity of estrogen receptor α or β, or of other nuclear receptors tested. Direct binding to ERRα was confirmed by a limited-proteolysis assay. The authors were explicit that the compound is not selective enough to separate the individual roles of the three ERR subtypes, because at active concentrations all three are switched on.
The same laboratories later developed a chemically distinct follow-up, SLU-PP-915, specifically because SLU-PP-332 lacks oral bioavailability (Billon et al., J Pharmacol Exp Ther 2026).
What is known about its pharmacokinetics
There are no human pharmacokinetic data. The available numbers are from mice and from in vitro liver preparations:
| Measurement | Result | Source |
|---|---|---|
| Tissue levels in mice, 2 h after a single injected dose | ≈0.6 μM in skeletal muscle, ≈0.2 μM in plasma | ACS Chem Biol 2023 |
| Human liver microsome half-life (in vitro) | 31.3 min; intrinsic clearance 22 μL/min/mg | Okda et al., Int J Biol Macromol 2026 |
| Kinetic aqueous solubility | 0.2 μM (very low; cLogP 4.05) | Okda et al., Int J Biol Macromol 2026 |
| Oral bioavailability | Described by the developers as lacking | J Pharmacol Exp Ther 2026 |
Two anti-doping laboratories have mapped how human liver enzymes break the molecule down, using liver S9 fractions and microsomes rather than volunteers. The UCLA Olympic Analytical Laboratory identified 22 metabolites, including five mono-hydroxylated and three di-hydroxylated products plus glucuronide and sulfate conjugates (Avliyakulov et al., Drug Test Anal 2026). The Cologne doping-control center reported nine metabolites, six Phase I and three Phase II (Möller et al., Rapid Commun Mass Spectrom 2026). Both groups did this work so that misuse could be detected in urine testing.
The very low solubility, the short microsomal half-life and the poor oral absorption are all reasons the original authors treated SLU-PP-332 as a research tool rather than a drug candidate. Note that the 24-hour figure listed for this compound in some reference tables, including this site’s own data file, is not supported by any published pharmacokinetic study in humans or animals.
What the research shows
All of the findings below are from animals or cells. None has been replicated in humans.
Exercise capacity in mice
In the original 2023 report, sedentary 3-month-old male mice were given SLU-PP-332 by intraperitoneal injection twice daily for 7 days and then run to exhaustion on a treadmill (Billon et al., ACS Chem Biol 2023):
| Outcome in mice | Result vs vehicle |
|---|---|
| Running time to exhaustion | ≈70% longer |
| Running distance | ≈45% further |
| Grip strength (after 2 weeks of treatment) | Increased |
| Type IIa oxidative muscle fibers in quadriceps | Increased |
| Mitochondrial DNA relative to nuclear DNA in muscle | Increased |
The effect depended on ERRα. Mice with ERRα deleted specifically in skeletal muscle gained no endurance from the compound, running the same distance as untreated knockout mice.
The gene-level comparison is the part most often misread. After a single dose, expression of two genes that acute aerobic exercise switches on, Ddit4 and Slc25a25, rose in muscle. For Ddit4, a 40-minute treadmill run produced roughly a 6-fold rise at 1 hour while the compound alone produced roughly a 3-fold rise; the two together produced an ≈11-fold rise. For Slc25a25, drug and exercise each produced an ≈11-fold rise. All of these effects had disappeared by 3 hours.
“Exercise in a pill” is not what the data show. In these experiments the compound reproduced part of an acute aerobic gene response, briefly, and worked best when combined with actual running. It was not tested against resistance training, it did not increase lean mass, and nothing like this has been measured in a human being.
Obesity and metabolic syndrome in mice
A follow-up paper studied normal-chow mice, diet-induced obese mice and leptin-deficient ob/ob mice, dosed by injection twice daily (Billon et al., J Pharmacol Exp Ther 2024):
| Model | Duration | Main findings |
|---|---|---|
| Normal chow, n = 8 per group | 28 days | No change in body weight, food intake or lean mass; less fat-mass gain; whole-body fatty acid oxidation ≈25% higher; energy expenditure higher; no change in glucose tolerance or insulin |
| Diet-induced obesity, n = 7 per group | 28 days | Treated mice weighed ≈12% less; controls gained ≈5 g of fat mass versus under 0.5 g in treated mice; lower total cholesterol, HDL and triglycerides; lower fasting glucose and insulin; improved glucose tolerance; less liver fat |
| ob/ob mice, n = 8 per group | 12–15 days | Body weight only trended down; fat mass and liver weight fell; fatty acid oxidation and resting energy expenditure rose; hepatic steatosis reduced |
Food intake did not change in any model, and the respiratory exchange ratio fell within 2 hours of the first dose, indicating a shift toward burning fat rather than carbohydrate. The authors reported only minor changes in plasma cholesterol and liver enzymes in chow-fed mice and no rise in liver enzymes in the obese model. HDL cholesterol fell along with total cholesterol in the obese mice, which the paper does not interpret as beneficial or harmful.
Heart failure in mice
In a pressure-overload model (transverse aortic constriction), mice were given SLU-PP-332 or the related compound SLU-PP-915 by injection twice daily for 6 weeks (Xu, Billon et al., Circulation 2024). Vehicle-treated mice saw ejection fraction fall to 33.8% at 6 weeks, versus 68.2% in sham-operated animals; SLU-PP-332 improved ejection fraction at weeks 4–6 and improved survival, without changing cardiac hypertrophy. SLU-PP-915 acted earlier and also improved stroke volume and cardiac output, which SLU-PP-332 did not. Knockdown experiments showed ERRγ was the main mediator of the cardiac effect.
Aging kidney in mice
Twenty-one-month-old mice treated for 8 weeks showed reduced albuminuria (protein leaking into urine), preserved podocyte numbers, better mitochondrial function and lower inflammatory markers, broadly resembling what lifelong caloric restriction did in the same study (Wang et al., Am J Pathol 2023).
Human cells, not human beings
The closest thing to human data is a pilot study of muscle biopsies from 20 women having hip replacement surgery. Myoblasts (immature muscle cells) from the inactive women were grown in culture and treated with SLU-PP-332. The treated cells showed higher SIRT1, PGC-1α, ERRα and FNDC5, lower NOX4, less oxidative stress and senescence, and more myotube formation (Bonanni et al., Front Physiol 2025). This is cell-culture work on human tissue, not treatment of patients.
A separate mechanistic paper found that ERR agonists induce the autophagy regulator TFEB in rat heart cells and in a mouse muscle cell line, one route by which ERR activation may remodel cells (Losby et al., Mol Pharmacol 2024).
What is not known about safety
There is no human safety data of any kind: no single-dose study, no dose-escalation study, no monitoring of liver, heart, blood counts or hormones in people. Statements about SLU-PP-332 being “safe” or “well tolerated” rest entirely on short mouse experiments.
What the mouse papers do report:
- No overt toxicity, normal complete blood counts and electrolytes, and no rise in creatine kinase after 10 days of twice-daily dosing (ACS Chem Biol 2023).
- Only minor changes in plasma cholesterol and liver enzymes over 28 days in chow-fed mice, and no liver-enzyme rise in diet-induced obese mice (J Pharmacol Exp Ther 2024).
- Falls in total cholesterol, HDL and triglycerides in obese mice. The long-term meaning of a lower HDL in this setting is not established.
- No change in circadian locomotor activity despite the compound altering clock-related gene expression in muscle.
Several real limitations follow from the pharmacology itself rather than from any observed harm:
- ERRs are expressed in heart, liver and kidney as well as skeletal muscle, and the compound cannot be aimed at one tissue or one subtype. The original authors note it is not selective enough to isolate a single ERR, so all three are activated at once. Longer-term consequences of that have not been characterized in any species.
- The longest published exposure is 8 weeks, in mice.
- Carcinogenicity, reproductive toxicity, immune effects and drug interactions have not been reported in any species.
Material sold as SLU-PP-332 is not made under pharmaceutical quality rules. The compound reaches research laboratories through chemical suppliers; the Cologne doping-control group, for example, bought theirs from a chemical reagent company (Möller et al., Rapid Commun Mass Spectrom 2026). Identity, purity and content of anything sold for other purposes are unverified.
Regulatory and anti-doping status
SLU-PP-332 is not approved for human use by the FDA, the EMA or any other regulator, and it is not named in the US Schedule III list of anabolic steroids and related substances (21 CFR 1308.13). It is a research chemical, not a controlled substance and not a dietary ingredient.
For athletes under the World Anti-Doping Code it is nonetheless prohibited. Class S0 of the WADA Prohibited List covers “any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use,” including drugs in preclinical development, and those substances are prohibited at all times, in and out of competition (WADA 2026 Prohibited List). SLU-PP-332 is not named individually. The related metabolic modulators in class S4.4 that are named include AMPK activators such as AICAR and MOTS-c, the PPARδ agonist GW501516, and the Rev-erbα agonists SR9009 and SR9011. Two accredited anti-doping laboratories have already published the metabolite patterns needed to detect SLU-PP-332 in urine.
Key takeaways
- No human data at all. Every reported effect is from mice, rat cardiomyocytes or cell culture. There are no published human trials and no human pharmacokinetic or safety data.
- It targets a nuclear receptor, not a hormone receptor. SLU-PP-332 activates ERRα, ERRβ and ERRγ, with ERRα EC50 of 98 nM. It is not a steroid, a SARM or a peptide, and it does not act on estrogen or androgen receptors.
- In mice it improved endurance, not size. Treated mice ran ≈70% longer and gained oxidative type IIa fibers, but lean mass did not increase, and the acute “exercise” gene response lasted only hours and was largest when combined with actual running.
- Its drug-like properties are poor. The developers report that it is not orally bioavailable, has very low solubility and a 31-minute human liver microsome half-life, which is why they built a successor compound, SLU-PP-915.
- Prohibited in sport, unapproved everywhere. It falls under WADA class S0 as a non-approved substance and is detectable through published metabolite methods, while remaining outside the US controlled-substance schedules.
Sources
- 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. PubMed; 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. PubMed; PMC.
- Xu W, Billon C, Li H, et al. Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation. 2024;149(3):227–250. PubMed; PMC.
- Wang XX, Myakala K, Libby AE, et al. Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney. Am J Pathol. 2023;193(12):1969–1987. PubMed; PMC.
- 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. PubMed.
- Okda HE, Zhao P, Hayes M, et al. Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling. Int J Biol Macromol. 2026;355:151450. PubMed; PMC.
- 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. PubMed.
- Möller T, Krug O, Thevis M. 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;40(8):e70039. PubMed; PMC.
- Bonanni R, Falvino A, Matticari A, et al. Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. Front Physiol. 2025;16:1616693. PubMed; PMC.
- Losby M, Hayes M, Valfort A, et al. The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB. Mol Pharmacol. 2024;106(4):164–172. PubMed; PMC.
- Hampton CS, Sitaula S, Billon C, et al. Development and pharmacological evaluation of a new chemical series of potent pan-ERR agonists, identification of SLU-PP-915. Eur J Med Chem. 2023;258:115582. PubMed; PMC.
- National Center for Biotechnology Information. SLU-PP-332, PubChem CID 5338394. PubChem.
- World Anti-Doping Agency. The 2026 Prohibited List, in effect 1 January 2026 (classes S0 and S4.4). WADA 2026 Prohibited List.
- Drug Enforcement Administration. Schedule III controlled substances, 21 CFR 1308.13. eCFR.
- National Library of Medicine. ClinicalTrials.gov registry search for SLU-PP-332 (no registered studies, searched October 2026). ClinicalTrials.gov.