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SLU-PP-332

A small-molecule activator of the ERR family of nuclear receptors (not a peptide), called an exercise mimetic because it increased running endurance and reduced fat gain in mice; no human trial has been registered, nothing containing it is approved, and it does not appear on any FDA 503A compounding list.

Data refreshed 2026-09-23 · Based on 8 published references

Names

Also called: SLU PP 332, SLUPP332, ERR pan-agonist 332, 4-hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide

Regulatory (US)

FDA approval: none

503A compounding: unknown

Molecule

Formula: C18H14N2O2

MW: 290.3 g/mol

CAS: 303760-60-3

PubChem entry

Origin

Discovered by: Cyrielle Billon, John K. Walker, Bahaa Elgendy, Thomas P. Burris and colleagues (Saint Louis University; Washington University School of Medicine and St. Louis College of Pharmacy; Salk Institute collaborators)

Year: 2023

What it is

SLU-PP-332 is not a peptide. It is a small synthetic chemical, listed on this site because it is often discussed alongside peptides. It switches on a family of three proteins inside cells called estrogen-related receptors, or ERRs. Despite the name, they do not respond to estrogen. They act like master switches for genes that build mitochondria, the parts of the cell that burn fat and sugar for energy, and they are central to how muscle adapts to endurance exercise.

Because it pushed mouse muscle toward a more endurance-trained state, its developers call it an “exercise mimetic”. So far it has been studied only in cells and in mice. It has never been tested in people, and no medicine containing it is approved.

SLU-PP-332 is 4-hydroxy-N’-[(E)-naphthalen-2-ylmethylidene]benzohydrazide (C18H14N2O2, 290.3 g/mol), an acylhydrazone agonist of the estrogen-related receptors ERRα, ERRβ and ERRγ (NR3B1–3). The ERRs are constitutively active orphan nuclear receptors with no identified endogenous ligand; together with the coactivator PGC-1α they drive transcription of genes for mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation and the Krebs cycle.

Billon et al. (2023) reported EC50 values of 98 nM at ERRα, 230 nM at ERRβ and 430 nM at ERRγ, making it a pan-agonist with the highest potency at ERRα. It increased mitochondrial respiration in C2C12 muscle cells and induced an acute aerobic-exercise gene programme in mouse muscle that depended on ERRα. In the heart-failure work, ERRγ was the main mediator of its transcriptional and protective effects.

Pharmacokinetics: two hours after 30 mg/kg intraperitoneally in mice, concentrations were about 0.6 µM in skeletal muscle and 0.2 µM in plasma. The developers later described it as lacking oral bioavailability. In pooled human liver S9 fractions it formed 22 metabolites, hydroxylated, reduced, glucuronidated or sulfated (Avliyakulov et al., 2026). No human data exist.

Who made it and when

SLU-PP-332 was designed by a team of chemists and pharmacologists in St. Louis, Missouri, led by Thomas Burris and working with Cyrielle Billon, John Walker and Bahaa Elgendy. The “SLU” prefix matches Saint Louis University, one of the institutions involved. They started from an older research compound that switched on only two of the three ERRs and redesigned it until it also switched on the third, ERR-alpha, which the team found was needed for the endurance effect in mice.

The first full report appeared in 2023, followed by mouse studies in obesity in 2024 and in heart failure in 2024. Some of the researchers hold shares in or co-founded small companies working on ERR drugs, but no company is known to have taken SLU-PP-332 itself into human testing.

Using structure-based design, the group optimised the ERRβ/γ-selective agonist scaffold GSK4716 for ERRα activity, gaining roughly 50-fold ERRα potency (Billon et al., ACS Chem Biol 2023; Saint Louis University, Washington University School of Medicine and St. Louis College of Pharmacy, Salk Institute and others). Follow-up papers covered diet-induced and genetic obesity (J Pharmacol Exp Ther 2024) and pressure-overload heart failure, together with a second pan-agonist, SLU-PP-915 (Xu, Billon et al., Circulation 2024). A 2026 paper described SLU-PP-915 as the orally active successor.

Disclosures: in the 2023 paper, Burris, Elgendy and Walker reported holding stock in Myonid Therapeutics, which works on ERR-based therapeutics. The Circulation paper discloses that co-author L. Zhang (Baylor) co-founded Pelagos Pharmaceuticals; a March 2024 American Chemical Society press release said Elgendy (Washington University School of Medicine) and colleagues hoped to test newer ERR agonists in animal models through Pelagos, a startup they had co-founded; and the 2026 SLU-PP-915 paper discloses that Burris holds stock in both Myonid and Pelagos, which it describes as developing ERR agonists, and that SLU-PP-915 is Saint Louis University intellectual property. No licence of SLU-PP-332 itself, no IND and no patent specific to it could be verified for this article.

What the data say

In mice, a week of twice-daily injections made the animals run about 70% longer and 45% farther on a treadmill before tiring, and about two weeks of injections shifted their muscle toward fatigue-resistant, oxygen-using fibres. In obese mice, it raised energy use and fat burning, reduced fat gain and improved blood-sugar control. In mice with a strained, failing heart, it improved heart pumping and survival.

All of this is from cells and mice, much of it from one collaborating group. No human has received it in a registered study, so nothing is known about its effects or safety in people. Anti-doping laboratories have already begun mapping how the body breaks it down so that it can be detected in sport.

Exercise capacity: in 12-week-old male C57BL/6J mice (n=6 per group) given 50 mg/kg intraperitoneally twice daily, 7 days of treatment increased running time by about 70% and distance by about 45% versus vehicle; 15 days of treatment increased type IIa oxidative fibres. Enhanced endurance required ERRα (Billon et al., 2023).

Metabolic disease: in diet-induced obese and ob/ob mice, SLU-PP-332 increased energy expenditure and fatty acid oxidation, reduced fat mass accumulation and improved insulin sensitivity (Billon et al., 2024).

Heart failure: in a pressure-overload heart-failure model, SLU-PP-332 and SLU-PP-915 improved ejection fraction, reduced fibrosis and increased survival without changing hypertrophy; metabolomics showed normalisation of fatty acid and oxidative phosphorylation metabolites, and genetic studies identified ERRγ as the main mediator (Xu et al., 2024).

Human data: none. ClinicalTrials.gov lists no study of SLU-PP-332. No repeat-dose toxicology, genotoxicity or safety pharmacology studies have been published. Two 2026 studies, from a UCLA group (Avliyakulov et al.) and Möller et al. (Rapid Commun Mass Spectrom), characterised metabolites specifically for doping control.

Regulatory picture

Three separate facts. Approval: no medicine containing SLU-PP-332 is approved by the FDA or any other regulator, and no company is known to be developing it for people. Compounding: it does not appear anywhere on the FDA’s lists for pharmacy compounding, neither the approved ingredients list nor the three categories of nominated substances, so it has never been assessed for that use. Enforcement: no FDA warning letter naming SLU-PP-332 was found. Sport: anti-doping scientists describe it as having doping potential and have published work to help detect it. Sale as a “research chemical” does not mean it has been evaluated for safety in people.

Approval: none. No IND-stage programme, NDA or foreign marketing authorisation could be identified, and no study is registered on ClinicalTrials.gov.

Compounding: SLU-PP-332 is not on the 503A bulks list in 21 CFR 216.23 and does not appear in Category 1, 2 or 3 of FDA’s list of substances nominated under section 503A (updated 2026-05-14), nor on FDA’s page of bulk drug substances that may present significant safety risks (updated 2026-04-22). It is not a component of any FDA-approved drug. Because it has not been evaluated under any of these pathways, this article records compounding status as unknown.

Enforcement: no FDA warning letter naming SLU-PP-332 was found in searches for this article.

Sport: Avliyakulov et al. (Drug Test Anal 2026) note that WADA prohibits exercise mimetics and metabolic modulators as a class; a named listing of SLU-PP-332 on the Prohibited List was not verified for this article. Metabolite studies were published in 2026 to support detection in doping control.

Doses reported in trials

Doses reported in studies, exactly as the cited trial reported them. They are not personal dosing instructions. Population, route and schedule matter more than the number.

No trials catalogued yet for this page.

Reported side effects

Not catalogued yet.

Interactions

Not catalogued yet.

Contraindications

Not catalogued yet.

Storage

No approved product exists, so there is no label storage data. Chemical suppliers publish their own storage statements; those are supplier claims, not verified data.

Product characteristics

Form: Synthetic small molecule (an aryl acylhydrazone), supplied as a research chemical powder

Stability: Its developers describe it as lacking oral bioavailability; published mouse studies gave it by intraperitoneal injection (Billon et al., 2026)

Compound information

Synthetic small molecule, not a peptide. No safety data sheet from a regulated drug manufacturer was found. No dedicated toxicology studies and no human pharmacokinetic data were found.

References

This page summarises the published sources below. PeptideBasics101 does no original research. Trial doses and results are reported as the cited study or label reported them. Sources can themselves be wrong or superseded; if you find a statement here that does not match its source, please tell us through our corrections process. Sources were last checked on 2026-09-23.

  1. Billon C et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol 2023 (pubmed.ncbi.nlm.nih.gov)
  2. Billon C et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther 2024 (pubmed.ncbi.nlm.nih.gov)
  3. Xu W, Billon C et al. Novel pan-ERR agonists ameliorate heart failure through enhancing cardiac fatty acid metabolism and mitochondrial function. Circulation 2024 (pubmed.ncbi.nlm.nih.gov)
  4. Billon C et al. An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. J Pharmacol Exp Ther 2026 (pubmed.ncbi.nlm.nih.gov)
  5. Avliyakulov NK et al. Analysis and identification of in vitro metabolites of exercise mimetic SLU-PP-332 for doping-control purposes. Drug Test Anal 2026 (pubmed.ncbi.nlm.nih.gov)
  6. American Chemical Society press release (EurekAlert!): Exercise in a pill: design and synthesis of novel ERR agonists as exercise mimetics (March 18, 2024) (eurekalert.org)
  7. FDA: bulk drug substances nominated for use in compounding under section 503A (categories 1–3, updated May 14, 2026) (fda.gov)
  8. PubChem: SLU-PP-332 (CID 5338394) (pubchem.ncbi.nlm.nih.gov)

Clinical trial entries in the table above link to their ClinicalTrials.gov registry records. Spotted an error? See corrections.

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