SLU-PP-332, known as an exercise mimetic – how does it work?

SLU-PP-332 was added to the Prohibited List by name before anyone had given it to a human being in a clinical trial. PubMed holds a dozen or so papers on it, ClinicalTrials.gov not a single study, and yet from 1 January 2027 it sits beside meldonium and trimetazidine in the class of metabolic modulators. That sequence of events says more about the compound than the slogan “exercise in a pill” that has clung to it since the 2023 publications.

This article explains what the molecule is, where the exercise-mimetic label came from, what mice and cell cultures showed, why the absence of human studies is a fact rather than a gap to be filled next year, and how regulators and anti-doping agencies read it. We transfer no figures from research protocols to anything beyond the models; the FAQ section explains why.

In our catalogue, the compounds discussed in this article are chemical reagents intended solely for laboratory research (Research Use Only). They are not medicinal products, dietary supplements or foods, and they are not intended for use in humans or animals. What this status means is explained in our material on the legal status of research reagents.

What SLU-PP-332 is

It is a small synthetic molecule, a hydrazone built from a 4-hydroxybenzoic acid residue and a naphthalene aldehyde: formula C₁₈H₁₄N₂O₂, mass 290.3 g/mol (PubChem CID 5338394). The name comes from Saint Louis University, where Thomas Burris’s team designed it using a structure-based approach. The first description appeared in 2023: the compound proved to be an agonist of all three ERR receptors (α, β and γ), most potent at ERRα, with “sufficient pharmacokinetic properties to be used as an in vivo chemical tool” (Billon et al., 2023, PMID 36988910).

ERRs are nuclear receptors related to the oestrogen receptor but unable to bind oestrogens, hence the label “orphan”. They govern the genes of mitochondrial biogenesis, oxidative phosphorylation, fatty acid oxidation and the Krebs cycle, and in skeletal muscle they mediate adaptation to aerobic exercise (Billon et al., 2026, PMID 41421047). For years there was no ERRα agonist fit for use in animals; SLU-PP-332 filled that gap as a chemical probe, a tool for studying the receptor rather than a drug candidate. A 2026 paper calls it a “widely used chemical probe for ERR activation” and only now describes a systematic structure–activity analysis of its scaffold (Okda et al., 2026, PMID 41850449).

Where the “exercise mimetic” label came from

The term comes straight from the first publication. In a muscle cell line SLU-PP-332 increased mitochondrial function and cellular respiration, and in mice it raised the proportion of type IIa (oxidative) fibres and lengthened running time to exhaustion. The authors showed that the compound switches on a gene programme in muscle that is characteristic of acute aerobic exercise and that this depends on ERRα: without the receptor, the endurance effect vanished (Billon et al., 2023). The programme includes the gene Ddit4, whose expression after the compound matched or exceeded that after treadmill running (Billon et al., 2026).

That is where the fact ends and the shorthand begins. Exercise changes hundreds of pathways at once: muscle vascularisation, insulin sensitivity in the liver and adipose tissue, the nervous system, bone. A 2025 review co-authored by the originators of the “hallmarks of ageing” concept lists more than a dozen such hallmarks that regular physical activity acts upon (Qiu et al., 2025, PMID 41352451). An agonist of a single receptor copies one of those programmes. How far that reaches is shown by a study unrelated to SLU-PP-332: overexpression of ERRγ in the muscle of obese db/db mice produced a full “aerobic” remodelling of fibres and vessels, yet improved neither energy expenditure nor insulin resistance (Badin et al., 2016, PMID 27220353). An exercise-like effect in muscle need not mean a metabolic effect in the body.

What the models showed

The St Louis team’s second step concerned metabolic syndrome. In diet-induced obese mice and in ob/ob mice the compound increased energy expenditure and fatty acid oxidation, limited fat mass accumulation and improved insulin sensitivity (Billon et al., 2024, PMID 37739806). Most headlines about a “weight-loss drug” rest on this paper, although the authors themselves write of mouse models and a promising direction, not of a result in humans.

The heart was studied in a model of heart failure from pressure overload. Both SLU-PP-332 and the chemically distinct SLU-PP-915 improved ejection fraction, reduced fibrosis and increased survival in mice without affecting cardiac hypertrophy; transcriptome and metabolome analyses showed normalisation of fatty acid and oxidative phosphorylation pathways (Xu et al., 2024, PMID 37961903). The same group described an autophagy mechanism: the gene for the transcription factor TFEB proved to be a direct ERR target, and the agonists raised its expression in cardiomyocytes and myoblasts (Losby et al., 2024, PMID 39168657).

The kidney was studied in 21-month-old mice, which are old animals. Eight weeks of treatment reversed the age-related albuminuria, podocyte loss, mitochondrial dysfunction and the rise in inflammatory cytokines, much as lifelong caloric restriction does; in both humans and mice, renal ERR expression declines with age (Wang et al., 2023, PMID 37717940). The only work with human material is a pilot study on myoblasts isolated from the muscle of 20 women undergoing hip surgery for osteoarthritis; the cells were treated with the compound in culture, not the patients (Bonanni et al., 2025, PMID 40692696). The common denominator of the whole literature: rodents and laboratory glassware, and in most papers the same group of authors.

What is missing: human studies

There are none. The ClinicalTrials.gov registry holds no study of SLU-PP-332 or SLU-PP-915 (queried on 7 November 2026). A 2026 systematic review covering the literature from 2020 to 2024 found only animal and cell work and closed with the sentence that clinical trials are needed to confirm efficacy and safety (de Souza-Lima et al., 2026, PMID 42024694). A review of nuclear receptor pharmacology from the same year lists ERRα agonists among compounds that “show promise in preclinical obesity models” (Di Giovanni and Lavecchia, 2026, PMID 41750342).

The team that created SLU-PP-332 is already working on a successor. SLU-PP-915 has a different scaffold, with a boronic acid moiety, and was selected from a series of 2,5-disubstituted thiophenes as a pan-agonist with better metabolic stability (Hampton et al., 2023, PMID 37421886); in 2026 it was described as having comparable exercise-mimetic activity in mice (Billon et al., 2026). For the reader this means that its creators treat SLU-PP-332 itself as an intermediate step. If any molecule of this family ever reaches human trials, it is more likely to be its successor.

The lack of human data has practical consequences. Nobody knows how SLU-PP-332 is metabolised in the human body, what its adverse effects are, or whether long-term activation of ERRs in every tissue at once is harmless. The only data on human metabolism come from a test tube: incubation with human liver S9 fraction identified 22 metabolites, including hydroxylated, glucuronidated and sulfated ones (Avliyakulov et al., 2026, PMID 41688415), while a second laboratory described nine (Möller et al., 2026, PMID 41588687). Both papers came from anti-doping laboratories and serve detection, not safety assessment.

The “pill instead of training” myth

The phrase “exercise in a pill” took off after a university press release in 2023 and keeps returning in vendors’ descriptions. In the literature, “exercise mimetic” means something narrower: a compound that, in a model, triggers part of the molecular response to exercise. The first paper showed longer running to exhaustion in mice, and the 2026 paper speaks of SLU-PP-915 synergising with training, not replacing it (Billon et al., 2026). Nobody has shown that any ERR agonist gives the body what regular movement gives it: adaptation of the circulation, bone, balance and mood.

The second myth is “fat burner”. A fall in fat mass was described in obese mice after weeks of treatment (Billon et al., 2024). That is a result in an animal model, obtained with a chemical tool that has not even passed the toxicology studies required before a first dose in humans. How to read results for this class of compounds against other mechanisms is explained in our guide to fat burners, and the place of SLU-PP-332 among compounds with preclinical data only is shown in our ranking by level of evidence. A related topic, the mitochondrial peptide from the same class of the WADA List, is covered in our article on MOTS-c.

Regulatory status

United States. No approval of SLU-PP-332 as a medicine is known in any country. The Drugs@FDA database lists no product containing this substance (checked 7 November 2026). FDA’s National Drug Code directory carries four listings of SLU-PP-332 as a bulk ingredient from manufacturers in China, India and the United States; such a listing is an identifier assigned at a company’s request, not an evaluation or approval by the agency.

European Union. The compound is absent from the EU medicines data that EMA publishes under Article 57 (data as of 9 October 2026). Nor does it have authorisation as a food or food supplement ingredient.

Other countries. We did not check registers outside the United States and the EU, and no approval is known to us. The reagent in our catalogue is material for laboratory research and may be described only as such. The identity and purity of a batch are confirmed by an analytical document; how to read it is explained in our article on the certificate of analysis. The wider context of compounds studied in connection with ageing and metabolism is given in our longevity guide.

Anti-doping note: two editions of the List

The 2026 Prohibited List, in force until 31 December 2026, does not name SLU-PP-332. Class S0 decides: “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” is prohibited at all times (2026 List). SLU-PP-332 meets that condition, so in 2026 it falls under S0.

The 2027 List, in force from 1 January 2027, moves it to class S4 (hormone and metabolic modulators). In subclass S4.4.1, metabolic modulators, alongside AMPK activators, PPARδ agonists and Rev-Erb-α agonists, a new bullet appears: “SLU-PP-332, SLU-PP-915 and related substances”. WADA’s explanatory note describes them as “examples of metabolic modulators acting in particular on oxidative metabolism” (2027 List and Summary of Major Modifications). The prohibition applies at all times, in and out of competition. One thing changes: substances in S4.4 are “non-specified”, whereas S0 covers specified substances, which matters for sanctioning rather than for the prohibition itself. Athletes tested in the United States fall under the same List, because USADA is a signatory to the World Anti-Doping Code. The classification rules, including the difference between the classes, are set out in our guide to the WADA Prohibited List; the final word rests with WADA and the national agencies.

Frequently asked questions

What is SLU-PP-332?
A synthetic small molecule from Saint Louis University, an agonist of the nuclear receptors ERRα, β and γ, described in 2023 as a chemical tool for studying those receptors in rodents. In mouse muscle it switches on a gene programme resembling the response to aerobic exercise.

Is SLU-PP-332 “exercise in a pill”?
No. It copies one ERRα-dependent gene programme in muscle. Exercise acts on more than a dozen processes at once, and a study in obese mice showed that “aerobic” remodelling of muscle alone did not improve their insulin resistance.

Has SLU-PP-332 been studied in humans?
No. ClinicalTrials.gov holds no study (7 November 2026), and a 2026 systematic review found only animal and cell work. The only human cells were treated with the compound in culture.

How does SLU-PP-915 differ from SLU-PP-332?
It is a chemically distinct agonist of the same receptors, with a boronic acid moiety, created by the same team as a successor. Both compounds are named on the 2027 List.

Why do we give no concentrations or schedules from the studies?
Because all of them come from protocols in mice and cell cultures, and the reagent in our catalogue is laboratory material that is not administered to humans or animals outside a study. Transferring those figures to a person has no basis whatsoever.

Is SLU-PP-332 prohibited in sport?
Yes, in both editions of the List. In 2026 it falls under class S0 as a substance without approval, and from 1 January 2027 it is named in class S4.4.1, metabolic modulators. The prohibition applies at all times.

Summary

SLU-PP-332 is a chemical probe that for the first time made it possible to activate the ERRα receptor in living animals. In mice it switches on the aerobic-exercise programme in muscle, lengthens running, reduces fat in obesity models, improves cardiac function in heart failure and kidney function in old animals. All of these data come from rodents and cell cultures, mostly from a single team, and there are no human studies, nor is any registered. No approval as a medicine is known in any country; the NDC listings in the United States concern bulk substance and are not an approval. The 2026 WADA List covers it under class S0, the 2027 List names it in S4.4.1. If this class of compounds ever reaches the clinic, it is more likely to be its successor, SLU-PP-915.

Product documentation

Reagent pages with batch documentation: SLU-PP-332 100 mcg, SLU-PP-332 PLUS 500 mcg and SLU-PP-332 MAX PLUS 1000 mcg. Compounds studied in lipid-metabolism models are collected in the fat burners category, and the wider overview is the category of compounds studied in the context of metabolism. The identity and purity of each batch are confirmed by a certificate of analysis.

Bibliography

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