# SLU-PP-332 and ERR exercise mimetics

Rating: Early — Mostly animal or cell studies; few or uncontrolled human data
Type: Compound
Updated: 2026-10-26
Canonical: https://heretic.bio/articles/slu-pp-332-and-err-exercise-mimetics.html

> SLU-PP-332 is a synthetic drug that switches on estrogen-related receptors (ERRs), which drive the muscle and mitochondrial response to aerobic exercise. In mice it increased endurance and oxidative muscle fibers, cut fat gain and improved insulin sensitivity, reversed features of kidney aging and improved survival in heart failure. No human has taken it in a published trial, the original compound is not orally bioavailable, most of the research comes from inventors with company stakes, and WADA names it on its 2027 Prohibited List.

> Estrogen-related receptors (ERRα/β/γ) are a plausible transcriptional node for aerobic-exercise adaptation. SLU-PP-332 is a synthetic pan-ERR agonist with mouse data for endurance, fat mass, insulin sensitivity, aged kidney, and pressure-overload heart failure. That is not a human exercise substitute. The published in vivo efficacy is murine, the original tool compound is not orally bioavailable, the inventors hold equity in companies developing the class, and anti-doping labs mapped its metabolites in 2026 because of its potential for misuse in sport.

For the training this compound tries to imitate, see [Exercise Science and Longevity](exercise-science-and-longevity.html); for the biology it targets, [Mitochondrial Health](mitochondrial-health.html). SLU-PP-332 is a small molecule, not a peptide, not a [senolytic](senolytics.html) and not an AMPK activator ([mTOR and AMPK Pathways](mtor-and-ampk-pathways.html)). Drug classes with far more human outcome data, such as [SGLT2 inhibitors](sglt2-inhibitors-as-senotherapeutics-evidence-taxonomy.html), are the fairer comparison.

## What the target is

ERRα, ERRβ, and ERRγ are orphan nuclear receptors. They are not estrogen receptors. Genetic work ties them to skeletal-muscle oxidative capacity, mitochondrial biogenesis, fatty-acid oxidation, and the Krebs cycle. Designing an agonist with useful ERRα activity, and with pharmacokinetics that survive in a live animal, was the practical bottleneck. SLU-PP-332 was reported as a pan-agonist with highest potency at ERRα and enough exposure to use as an in vivo tool ([PMID 36988910](https://pubmed.ncbi.nlm.nih.gov/36988910/)).

A later, chemically distinct pan-agonist, **SLU-PP-915** , was built because SLU-PP-332 lacks oral bioavailability. SLU-PP-915 is orally bioavailable and, in mice, matches the intraperitoneal endurance effect of SLU-PP-332 when dose is adjusted for systemic exposure ([PMID 41421047](https://pubmed.ncbi.nlm.nih.gov/41421047/)).

Neither compound has an approved drug name or a registered human trial (ClinicalTrials.gov, October 2026). Both are investigational research compounds, not supplements.

## Evidence taxonomy

Setting | Model | What was actually shown | What was not shown  
---|---|---|---  
Cell | Skeletal-muscle cell line | Higher mitochondrial function and cellular respiration ([PMID 36988910](https://pubmed.ncbi.nlm.nih.gov/36988910/)) | Human dosing, safety, or performance  
Mouse, acute/subchronic | Wild-type mice | More type IIa oxidative fibers; longer exercise endurance; an ERRα-dependent acute aerobic gene program. ERRα activation was required for the endurance effect | That the same program runs in people, or that it replaces training  
Mouse, obesity | Diet-induced obese and ob/ob | Higher energy expenditure and fatty-acid oxidation, less fat-mass accumulation, less obesity, better insulin sensitivity ([PMID 37739806](https://pubmed.ncbi.nlm.nih.gov/37739806/)) | Magnitude in humans; lean-mass preservation; hard outcomes  
Mouse, aged kidney | 21-month-old mice, 8 weeks | Reversal of age-related albuminuria, podocyte loss, mitochondrial dysfunction, and inflammatory cytokines, via cGAS-STING and STAT3. ERRs were lower in aging human and mouse kidney and preserved by lifelong caloric restriction ([PMID 37717940](https://pubmed.ncbi.nlm.nih.gov/37717940/)) | A human kidney trial  
Mouse, heart failure | Pressure-overload HF | SLU-PP-332 and SLU-PP-915 both improved ejection fraction, reduced fibrosis, and increased survival without changing hypertrophy. Metabolomics moved fatty-acid/lipid and TCA/oxidative-phosphorylation profiles toward normal ([PMID 37961903](https://pubmed.ncbi.nlm.nih.gov/37961903/)) | A human heart-failure trial  
Human tissue, ex vivo | Myoblasts from 10 inactive women (hip arthroplasty cohort, n=20 total) | In culture, SLU-PP-332 lowered NOX4 and raised SIRT1, PGC-1α, ERRα, FNDC5, Akt, and Bcl-2; less cytotoxicity, oxidative stress, and senescence markers; more myotube formation ([PMID 40692696](https://pubmed.ncbi.nlm.nih.gov/40692696/)) | Any ingested dose, any performance endpoint, any safety dataset  
Human liver fractions | Pooled human liver S9 | 22 phase I/II metabolites mapped for doping-control detection ([PMID 41688415](https://pubmed.ncbi.nlm.nih.gov/41688415/)) | In vivo human metabolite confirmation  
  
As of October 2026 no human efficacy, pharmacokinetic or safety trial of SLU-PP-332 or SLU-PP-915 has been published in PubMed or registered on ClinicalTrials.gov.

## Mouse findings

### Endurance: the paper the "exercise in a pill" claim rests on

Billon et al., _ACS Chemical Biology_ 2023 ([PMID 36988910](https://pubmed.ncbi.nlm.nih.gov/36988910/); [PMC11584170](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584170/)):

  * SLU-PP-332 targets all three ERRs, highest potency at ERRα.
  * In mice it increased type IIa oxidative skeletal-muscle fibers and enhanced exercise endurance.
  * The acute aerobic gene program was ERRα-specific, and ERRα activation was critical for the endurance gain.
  * The authors' own framing is a feasibility claim for metabolic disease and aging muscle, not a completed therapeutic.



**Conflict:** T.P. Burris, B. Elgendy, and J.K. Walker are stockholders in Myonid Therapeutics, Inc., which develops ERR therapeutics. Read the endurance paper as inventor science, not as an independent replication.

### Metabolic syndrome

Billon et al., _Journal of Pharmacology and Experimental Therapeutics_ 2024 ([PMID 37739806](https://pubmed.ncbi.nlm.nih.gov/37739806/); [PMC10801787](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801787/)): in diet-induced obese and ob/ob mice, SLU-PP-332 increased energy expenditure and fatty-acid oxidation and reduced fat-mass accumulation, with improved insulin sensitivity. The abstract does not report a human-equivalent dose, a lean-mass result, or a durability result after drug withdrawal.

### Aging kidney, and the caloric-restriction parallel

Wang et al., _American Journal of Pathology_ 2023 ([PMID 37717940](https://pubmed.ncbi.nlm.nih.gov/37717940/)):

  * ERRs were decreased in aging human kidney and aging mouse kidney.
  * Lifelong caloric restriction preserved ERR expression in aging mice.
  * Eight weeks of SLU-PP-332 in 21-month-old mice reversed age-related increases in albuminuria, podocyte loss, mitochondrial dysfunction, and inflammatory cytokines, through cGAS-STING and STAT3.
  * A three-week STING inhibitor (C-176) in the same age of mice also reversed inflammatory cytokines and the senescence marker p21/Cdkn1a, and unexpectedly restored PGC-1α, ERRα, mitochondrial complexes, and MCAD.



This is the strongest aging-biology paper on this page, and it is still a mouse treatment study plus an observational human-tissue expression finding. It does not show that an ERR agonist slows human kidney aging.

### Heart failure

Xu, Billon, et al., _Circulation_ 2024 ([PMID 37961903](https://pubmed.ncbi.nlm.nih.gov/37961903/)): both SLU-PP-332 and SLU-PP-915 improved ejection fraction, reduced fibrosis, and increased survival in pressure-overload heart failure, without affecting hypertrophy. A broad set of fatty-acid and mitochondrial genes was induced. Metabolomics after six weeks of pressure overload showed substantial normalization of fatty-acid/lipid and TCA/oxidative-phosphorylation metabolites. Genetic-dependency experiments identified ERRγ, not ERRα, as the main mediator of the heart benefit. One author is a cofounder of and consultant for Pelagos Pharmaceuticals, which develops ERR agonists.

### Oral follow-on: SLU-PP-915

Billon, Appourchaux, Côté, and Burris, _JPET_ 2026 ([PMID 41421047](https://pubmed.ncbi.nlm.nih.gov/41421047/)):

  * SLU-PP-332 improves aerobic performance in mice but **lacks oral bioavailability**.
  * SLU-PP-915 is orally bioavailable. Intraperitoneal 915 enhanced distance and duration to a similar extent as 332. Oral 915 kept comparable efficacy after adjustment for systemic exposure.
  * Both compounds induce _Ddit4_ (a gene induced by acute aerobic exercise), matching or exceeding treadmill running depending on the muscle examined.
  * 915 plus exercise training further increased _Ddit4_ and mitochondrial gene expression. That is synergy with training in mice, not a reason to skip training.



**Conflict:** SLU-PP-915 is covered by Saint Louis University intellectual property with Burris as an inventor. Burris is a stockholder in Myonid Therapeutics and Pelagos Pharmaceuticals, both active in ERR agonists.

A 2026 structure-activity study from the same group mapped which parts of the SLU-PP-332 scaffold control ERRα and ERRγ agonism and reported analogues with better solubility or metabolic stability; two of its authors (Elgendy, Burris) are Pelagos cofounders ([PMID 41850449](https://pubmed.ncbi.nlm.nih.gov/41850449/)). A 2026 Spanish-language review covers ERR activation as an exercise mimetic ([PMID 42024694](https://pubmed.ncbi.nlm.nih.gov/42024694/)).

## The only human biological data

Bonanni et al., _Frontiers in Physiology_ 2025 ([PMID 40692696](https://pubmed.ncbi.nlm.nih.gov/40692696/)), a pilot from an Italian group with no declared ties to the developers:

  * Twenty women undergoing hip arthroplasty for coxarthrosis, split by self-reported activity (10 active, 10 inactive).
  * Inactive muscle had higher NOX4 and lower SIRT1, PGC-1α, ERRα, and FNDC5, alongside worse handgrip and smaller fiber diameter in the clinical comparison.
  * Primary myoblasts from the inactive group, treated in culture with SLU-PP-332, showed lower NOX4 and higher SIRT1, PGC-1α, ERRα, FNDC5, Akt, and Bcl-2, with less cytotoxicity, oxidative stress, and senescence markers, higher reduced glutathione, and more myotube formation over 15 days of differentiation.



The authors' discussion is appropriately narrow: targeting ERRs might be a strategy against inactivity-related atrophy, and further work is required. This is not an oral human study. Self-reported activity and surgical muscle from osteoarthritic hips are a weak activity phenotype.

## Doping-control signal (2026)

Two analytical papers treat the class as a sports-doping problem rather than a clinic-ready drug:

  * Avliyakulov, Sobolevsky, and Ahrens, UCLA Olympic Analytical Laboratory, _Drug Testing and Analysis_ 2026 ([PMID 41688415](https://pubmed.ncbi.nlm.nih.gov/41688415/)). In pooled human liver S9 they identified five monohydroxylated metabolites (M1–M5), three dihydroxylated (M6–M8), four reduced dihydroxylated (M9–M12), plus direct glucuronide (M13) and sulfate (M19) of the parent, and hydroxylated conjugates (M14–M18, M20–M22). Most abundant, and flagged as potentially useful for detection: M1, M7, M9, M10, M13, M14, M19, M20. Structures are not fully solved. The paper notes that WADA prohibits exercise mimetics and metabolic modulators.
  * A second anti-doping lab, at the German Sport University Cologne, identified nine in vitro metabolites of SLU-PP-332 and seven of SLU-PP-915, and confirmed three of the 915 metabolites by synthesis and NMR ([PMID 41588687](https://pubmed.ncbi.nlm.nih.gov/41588687/)).



**Banned by name from 2027.** WADA's 2027 Prohibited List, in force from 1 January 2027, names "SLU-PP-332, SLU-PP-915 and related substances" under S4.4.1 metabolic modulators, prohibited at all times. Before that they fall under S0, non-approved substances ([WADA 2027 Prohibited List](https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf)).

Anti-doping labs build detection methods for compounds they expect athletes might misuse. That is a warning sign, not evidence that it works in athletes.

## Claims audit

Claim | Verdict | Why  
---|---|---  
"Exercise in a pill" | Unsupported as a human claim | Endurance data are murine. The oral analogue still has no human efficacy trial.  
ERR agonism can induce an acute aerobic gene program in mice, dependent on ERRα | Supported, one lab cluster | [PMID 36988910](https://pubmed.ncbi.nlm.nih.gov/36988910/), with inventor equity  
Improves obesity and insulin sensitivity | Mouse only | [PMID 37739806](https://pubmed.ncbi.nlm.nih.gov/37739806/). The abstract gives no effect sizes  
Reverses features of kidney aging | Mouse treatment; human tissue is expression-only | [PMID 37717940](https://pubmed.ncbi.nlm.nih.gov/37717940/)  
Treats heart failure | Mouse pressure-overload only | [PMID 37961903](https://pubmed.ncbi.nlm.nih.gov/37961903/)  
Safe to buy as a research chemical and dose like a supplement | Unsupported and outside the literature | No human PK, no human safety set, detection methods already published  
Replaces exercise | Not established | In mice, 915 added to the gene effects of training; no study has tested it as a replacement for training  
  
## Practical context

Not medical advice. No human dose has ever been studied, so none is given here, and mouse doses do not translate into a safe human amount.

  * Do not treat gray-market SLU-PP-332 as an exercise substitute. The compound the endurance paper used is not orally bioavailable ([PMID 41421047](https://pubmed.ncbi.nlm.nih.gov/41421047/)).
  * Tested athletes face a named ban from 1 January 2027 ([WADA 2027 list](https://www.wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf)), and anti-doping labs published metabolite maps in 2026 specifically to detect it ([PMID 41688415](https://pubmed.ncbi.nlm.nih.gov/41688415/)).
  * Inventor conflict is material: equity in Myonid (and, for 915, Pelagos) plus university IP. Independent replication is the missing piece, not another press summary of the same mouse studies.
  * If a human trial appears, the minimum useful readout is oral PK, a pre-registered exercise or metabolic endpoint, and adverse-event reporting. Gene-expression changes in a dish do not meet that bar.



## What to watch

  1. Whether a lab without ties to the developers reproduces the endurance effect in animals.
  2. Human oral pharmacokinetics and safety data for SLU-PP-915; none are published yet.
  3. Whether chronic pan-ERR agonism has liabilities the short mouse studies miss (cardiac hypertrophy was _not_ increased in the heart-failure model, which is reassuring and still not a chronic human safety study).
  4. Until human data exist, the class is a research watch item, not a substitute for [training](exercise-science-and-longevity.html).

## Sources

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;18(4):756-771. PMID 36988910 . DOI 10.1021/acschembio.2c00720 . PMC11584170 . (PubMed 36988910, PMC11584170, DOI 10.1021/acschembio.2c00720)
2. 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. PMID 41421047 . DOI 10.1016/j.jpet.2025.103787 . (PubMed 41421047, DOI 10.1016/j.jpet.2025.103787)
3. Billon C et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024;388(2):232-240. PMID 37739806 . DOI 10.1124/jpet.123.001733 . (PubMed 37739806, DOI 10.1124/jpet.123.001733)
4. Wang XX et al. Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney. Am J Pathol. 2023;193(12):1969-1987. PMID 37717940 . DOI 10.1016/j.ajpath.2023.07.008 . (PubMed 37717940, DOI 10.1016/j.ajpath.2023.07.008)
5. Xu W, Billon C, et al. Novel pan-ERR agonists ameliorate heart failure through enhancing cardiac fatty acid metabolism and mitochondrial function. Circulation. 2024;149(3):227-250. PMID 37961903 . DOI 10.1161/CIRCULATIONAHA.123.066542 . (PubMed 37961903, DOI 10.1161/CIRCULATIONAHA.123.066542)
6. Bonanni R et al. Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. Front Physiol. 2025;16:1616693. PMID 40692696 . DOI 10.3389/fphys.2025.1616693 . (PubMed 40692696, DOI 10.3389/fphys.2025.1616693)
7. Avliyakulov NK, Sobolevsky T, Ahrens E. Analysis and identification of in vitro metabolites of exercise mimetic SLU-PP-332 for doping-control purposes. Drug Test Anal. 2026;18(3):439-450. PMID 41688415 . DOI 10.1002/dta.70035 . (PubMed 41688415, DOI 10.1002/dta.70035)
8. PMC10801787 (PMC10801787)
9. Okda HE 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. PMID 41850449 . (PubMed 41850449)
10. de Souza-Lima J et al. Pharmacological activation of ERRα/β/γ as an exercise mimetic: potential therapeutic applications (in Spanish). Rev Med Chil. 2026. PMID 42024694 . (PubMed 42024694)
11. 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. PMID 41588687 . DOI 10.1002/rcm.70039 . (PubMed 41588687, DOI 10.1002/rcm.70039)