SLU-PP-332
A synthetic exercise mimetic that activates estrogen-related receptors (ERRs) to replicate the molecular effects of aerobic exercise — increasing endurance, fat oxidation, and mitochondrial function without physical activity.
What is SLU-PP-332?
SLU-PP-332 is a synthetic small-molecule agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ) developed by Thomas Burris's lab at Saint Louis University. It is not a peptide — it's a small molecule — but has gained significant attention in the performance and longevity community as an "exercise in a pill." In mice, SLU-PP-332 activates the same genetic program that aerobic exercise turns on: it increases fatigue-resistant type IIa muscle fibers, boosts mitochondrial function, increases energy expenditure, enhances fatty acid oxidation, and improves exercise endurance on treadmill tests. Beyond muscle, it has shown remarkable effects in heart failure (improved ejection fraction and survival, published in Circulation) and kidney aging. Anti-doping agencies are already developing detection methods — two papers on identifying SLU-PP-332 metabolites for doping control were published in 2026.
What SLU-PP-332 Is Investigated For
SLU-PP-332 is investigated as an exercise mimetic — specifically for endurance enhancement, metabolic syndrome, heart failure, age-related kidney dysfunction, and sarcopenia — and the strongest evidence to date is for heart failure in mouse pressure-overload models, where Circulation published improved ejection fraction, reduced fibrosis, and increased survival driven primarily by ERRγ. Supporting mouse data spans multi-organ ERR-mediated benefits: increased type IIa oxidative muscle fibers and treadmill endurance (ACS Chemical Biology 2023), metabolic syndrome reversal, and reversal of age-related kidney mitochondrial dysfunction. The honest caveats dominate the picture: all efficacy data is preclinical in mice, no human clinical trials have been conducted, and there is no validated human dose, pharmacokinetic profile, or safety framework. The compound is also not a peptide but a small molecule, chronic pan-ERR activation across multiple organ systems has unknown long-term consequences, and anti-doping laboratories published SLU-PP-332 metabolite detection methods in 2026 signaling imminent WADA listing.
History & Discovery
SLU-PP-332 was developed in the laboratory of Thomas Burris at Saint Louis University as a synthetic pan-agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ) — orphan nuclear receptors that serve as master transcriptional regulators of mitochondrial biogenesis, oxidative phosphorylation, and fatty acid metabolism. The Burris lab had spent years characterizing ERR pharmacology and recognized that the receptor family represented an unusually direct molecular handle on the genetic program activated by aerobic exercise. The headline ACS Chemical Biology paper (2023) showed that SLU-PP-332 activates an ERRα-dependent acute aerobic exercise transcriptional response in mouse skeletal muscle and enhances treadmill endurance. Subsequent papers extended the profile across organ systems: metabolic syndrome (J Pharmacol Exp Ther 2024), heart failure with improved ejection fraction and reduced fibrosis (Circulation 2024), age-related kidney mitochondrial dysfunction (2023), and pilot work in age-related muscle atrophy (2025). The 'exercise mimetic' framing has driven significant attention from longevity, performance, and obesity communities, and an orally active successor, SLU-PP-915, was published in 2026. Anti-doping researchers have already characterized SLU-PP-332 metabolites for detection (two 2026 papers), signaling imminent prohibition. Note that SLU-PP-332 is a small molecule, not a peptide — it is included on this site because it is widely discussed alongside performance and metabolic peptides in the optimization community.
How It Works
SLU-PP-332 activates a family of receptors called ERRs (estrogen-related receptors) that serve as master switches for the genes your body turns on during aerobic exercise. When activated, these receptors increase mitochondrial activity (your cells' power plants), shift muscle fibers toward the fatigue-resistant type used for endurance, and ramp up fat burning — producing many of the metabolic benefits of a workout without the physical activity.
SLU-PP-332 is a synthetic pan-agonist of estrogen-related receptors alpha, beta, and gamma (ERRα/β/γ), with highest potency for ERRα. ERRs are orphan nuclear receptors that regulate mitochondrial biogenesis, oxidative phosphorylation, and fatty acid metabolism — the core metabolic adaptations of aerobic exercise. In skeletal muscle, SLU-PP-332 induces an ERRα-dependent acute aerobic exercise genetic program, increasing type IIa oxidative muscle fibers and enhancing treadmill endurance in mice. It upregulates PGC-1α, SIRT1, ERRα, and FNDC5 (irisin precursor), while reducing lactate dehydrogenase release, ROS production, and cellular senescence markers. In metabolic syndrome models, it increased energy expenditure and fatty acid oxidation, reduced fat mass, and improved insulin sensitivity. In heart failure (pressure overload model), it significantly improved ejection fraction, reduced fibrosis, and increased survival — with ERRγ identified as the primary cardioprotective mediator. Multi-omics analysis confirmed activation of fatty acid metabolism and mitochondrial function gene networks. In aging kidney, it reversed mitochondrial dysfunction and inflammation.
Evidence Snapshot
Human Clinical Evidence
None. SLU-PP-332 has not entered human clinical trials. All evidence is from mouse models and cell culture. The next-generation orally active compound SLU-PP-915 may be closer to clinical development.
Animal / Preclinical
Strong and multi-organ. Exercise/muscle: increased type IIa oxidative fibers and enhanced treadmill endurance in mice (ACS Chemical Biology, 2023). Metabolic syndrome: reduced obesity, increased energy expenditure, improved insulin sensitivity in obese mice (J Pharmacol Exp Ther, 2024). Heart failure: improved ejection fraction, reduced fibrosis, increased survival in pressure overload model (Circulation, 2024). Kidney: reversed age-related mitochondrial dysfunction and inflammation (2023). Muscle atrophy: pilot study targeting age-related inactivity (2025).
Mechanistic Rationale
Strong. ERRs are well-established master regulators of mitochondrial biogenesis and oxidative metabolism. The connection between ERR activation and exercise adaptation is supported by extensive prior research on PGC-1α/ERR signaling. SLU-PP-332's effects are consistent with predicted ERR biology across multiple organ systems.
Research Gaps & Open Questions
What the current literature has not yet settled about SLU-PP-332:
- 01Human pharmacokinetics, oral bioavailability, dosing, and safety are entirely uncharacterized — no published Phase 1 trial exists for SLU-PP-332 or its successor SLU-PP-915.
- 02Whether mouse exercise-mimetic effects translate to clinically meaningful human endurance, body composition, or metabolic outcomes is unproven.
- 03Long-term safety of chronic pan-ERR activation in humans — ERRs regulate genes across cardiac, hepatic, renal, muscle, and metabolic tissues, and chronic agonism could have unintended effects.
- 04Relevance to clinical heart failure, where the mouse data are most striking, requires properly designed human trials of SLU-PP-915 or a successor.
- 05Whether SLU-PP-332 produces meaningful muscle hypertrophy or strength gains (as opposed to fiber-type shifts and endurance) is not supported by current data — it is more analogous to endurance training than resistance training.
- 06Combination with other longevity-targeted compounds (rapamycin, metformin, NAD+ precursors, GLP-1 agonists) is widely discussed but entirely unstudied.
Forms & Administration
SLU-PP-332 has been administered via intraperitoneal injection in mouse studies. An orally active next-generation compound, SLU-PP-915, has been developed and published in 2026. Neither is available for human use. These are strictly research compounds not available through legitimate medical channels.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
There is no human dose because SLU-PP-332 has not entered human clinical trials. Mouse studies have used intraperitoneal injection at doses in the 10–100 mg/kg/day range, with most published work clustering around 25–50 mg/kg/day. Allometric scaling to humans is fraught and the oral bioavailability of SLU-PP-332 itself is poor, which is the design motivation for the orally active successor SLU-PP-915.
Frequency
Mouse protocols have used daily intraperitoneal dosing over study durations of days to weeks. Human dosing schedules are not established because no clinical trials have been conducted.
Timing Considerations
Time of day
Ties to training schedule in the rodent protocols that generated the initial data; no human regimen is validated.
Relative to meals
Most rodent protocols used fasted dosing. Human practice is undefined.
Relative to exercise
Pre-workout is the most common pattern among self-experimenters, though the evidence base is preclinical and human data is essentially absent.
Cycle Length
There is no concept of a validated human cycle. Chronic ERR activation across multiple organ systems carries unknown long-term implications, and the published mouse studies are too short to characterize chronic safety in any species.
Protocol Notes
SLU-PP-332 is a research compound, not a clinical drug. It is sold by research-chemical suppliers for laboratory use only, and use in humans is unauthorized in every jurisdiction. The 'exercise in a pill' framing has driven a grey-market following, but this framing oversells the data — SLU-PP-332 replicates a portion of the molecular response to exercise, not the full multisystem effect, and all efficacy data come from mouse models. The orally active successor SLU-PP-915 is also strictly a research compound with no human exposure data. Anyone using SLU-PP-332 should understand that they are taking an unstudied small molecule outside any regulated pharmacovigilance framework, that ERRs regulate genes across cardiac, hepatic, renal, muscle, and metabolic tissues, and that the chronic effects of pan-ERR agonism in humans are entirely uncharacterized.
SLU-PP-332 is not approved for human use by any regulatory authority and has not been tested in human clinical trials. There is no validated human dose, no established safety profile, and no monitoring framework for users of grey-market material.
Timeline of Effects
Onset
In mouse studies, acute transcriptional responses (gene expression changes consistent with the aerobic exercise program) emerged within hours of dosing. Functional changes (enhanced treadmill endurance, body composition shifts, metabolic improvements) emerged over days to weeks of repeated dosing. No human onset data exist.
Peak Effect
Mouse protocols have run for days to weeks; whether effects continue to accumulate, plateau, or attenuate with chronic dosing is largely uncharacterized. Cardiac improvements in heart failure models accumulated over the study duration. No information exists on peak human effect because no humans have been studied.
After Discontinuation
Mechanistically, ERR-mediated transcriptional effects would be expected to fade within days to weeks of stopping the compound as gene expression returns to baseline. The functional consequences (mitochondrial biogenesis, fiber-type shifts) might persist longer due to the slower turnover of structural adaptations. No formal washout data exist in any species.
Monitoring & Measurement
Bloodwork & Labs
- •Lipid panel — ERR-alpha agonism shifts fatty-acid oxidation in rodent work, so triglycerides and HDL are the most reactive markers to watch
- •Fasting glucose, fasting insulin (HOMA-IR), HbA1c
- •ALT and AST — hepatic metabolism is plausibly affected; useful to track
- •CBC — anchor
Functional & Performance Tests
- •Time to exhaustion on a fixed submaximal workload (treadmill, bike, or rower) — the endurance endpoint the rodent work produced
- •VO2 max via lab test or validated wearable algorithm
- •DEXA scan — body composition
- •Resting heart rate and HRR (wearable)
When to Test
Baseline, 6 weeks, 12 weeks.
Interpretation & Notes
SLU-PP-332 has no published human trials as of 2026 — the entire evidence base is rodent. That makes honest measurement more important than usual: you are testing whether a compound with no human safety data or dose-response curve is doing anything in your case, and the answer is often no. Submaximal time-to-exhaustion is a more sensitive endurance endpoint than VO2 max. Metabolic shifts at 12 weeks (lipids, HOMA-IR) are the secondary readout and are less prone to training-effect confounding. SLU-PP-332 will be in scope for WADA detection in the near term; athletes subject to testing should not use it. Routine labs available direct-to-consumer; VO2 max via university sports-science programs or performance clinics.
Common Questions
Who SLU-PP-332 Is NOT For
- •Pregnancy and breastfeeding — no human safety data; ERRs regulate developmental gene expression and pan-ERR agonism during fetal or infant development carries unquantified risk.
- •Pediatric use — entirely unstudied; no plausible justification for use in a developing population.
- •Known cardiovascular disease — although mouse heart failure data show benefit, the same pharmacology in humans without supervision and with no monitoring framework is inappropriate. The cardiac data in mice are encouraging for the development of regulated therapeutics, not a justification for self-administration.
- •Active or recent-history cancer — ERRs (particularly ERRα) have documented roles in tumor metabolism and progression in several cancer contexts; chronic pan-ERR agonism in patients with malignancy carries theoretical risk that has not been studied.
- •Significant hepatic or renal impairment — first-pass metabolism, drug clearance, and the consequences of pan-ERR activation in compromised tissues are uncharacterized.
- •Athletes subject to anti-doping testing — beyond the prohibited-substance question, the metabolite-detection methods being published in 2026 will increase the probability of failed tests.
Drug & Supplement Interactions
Documented drug-interaction data for SLU-PP-332 in humans are nonexistent because no human clinical trials have been performed. Theoretical interactions follow from the pharmacology. Co-administration with metformin, AMPK activators, or other compounds affecting mitochondrial energy metabolism could produce additive or interfering effects on the same downstream pathways. Co-administration with other exercise-mimetic concepts (AMPK activators like AICAR, SIRT1 activators, mitochondrial cofactors) is widely discussed in optimization circles but entirely unstudied. The cardiac effects observed in mouse heart failure models raise theoretical interactions with conventional heart failure pharmacotherapy (ACE inhibitors, beta-blockers, SGLT2 inhibitors, ARNIs), where additive cardiac remodeling effects could occur but have not been characterized. Effects on drug-metabolizing enzymes (CYPs) and transporters have not been systematically studied. Anyone using SLU-PP-332 alongside chronic medications is doing so without any human pharmacokinetic data and should disclose use to their prescribing clinician.
Safety Profile
Common Side Effects
Cautions
- • Not approved for human use — strictly a research compound
- • No human clinical trials have been conducted
- • Anti-doping agencies are developing detection methods (likely to be prohibited in sports)
- • Gray market sources have unknown purity and composition
- • Long-term effects of chronic ERR activation are unknown
What We Don't Know
All data is from mouse models. Whether ERR agonism translates to meaningful exercise-like benefits in humans is unproven. Chronic pan-ERR activation could have unintended effects given that ERRs regulate genes across multiple organ systems. The next-generation compound SLU-PP-915 (orally active) may be more clinically relevant but also lacks human data.
Legal Status
United States
SLU-PP-332 is not FDA-approved, has no Investigational New Drug status, and is not in any active clinical trial. It is sold by research-chemical suppliers for laboratory research use only. Human use is unauthorized. The successor SLU-PP-915 is in the same regulatory position.
International
No regulatory authority in any jurisdiction has approved SLU-PP-332. Its availability is uniformly limited to research-chemical channels and is not authorized for human use anywhere.
Sports & Competition
SLU-PP-332 is not yet listed by name on the WADA Prohibited List, but anti-doping researchers have already characterized its metabolites specifically for detection (two 2026 papers in mass spectrometry journals), signaling imminent listing. WADA's S0 category (substances not approved by any government regulatory health authority for human therapeutic use) currently covers it, and the explicit listing under either S0, S2, or a stand-alone exercise-mimetic category is a near-term regulatory step. Athletes subject to WADA, USADA, or equivalent codes should treat SLU-PP-332 as prohibited in and out of competition.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
SLU-PP-332 is a peptide.
Reality
SLU-PP-332 is a small-molecule synthetic ERR agonist, not a peptide. It is included on this site because it is widely discussed alongside performance and metabolic peptides in the longevity and optimization community, but the molecule, mechanism, and class are entirely distinct from peptide hormone analogs.
Myth
SLU-PP-332 replicates the full benefits of exercise.
Reality
SLU-PP-332 activates a portion of the molecular response to aerobic exercise — ERR-mediated mitochondrial biogenesis, fatty acid oxidation, and oxidative fiber-type shifts. Exercise also produces cardiovascular adaptations, neurological effects, hormonal cascades, skeletal loading, and dozens of other downstream consequences that ERR activation does not replicate. SLU-PP-332 is being studied primarily as a therapeutic for people who cannot exercise (heart failure, severe obesity, immobility), not as a substitute for exercise in healthy individuals.
Myth
Because the published data come from a respected academic lab and reputable journals, SLU-PP-332 is safe for human use.
Reality
The published data are preclinical and exclusively in mouse models. The quality and rigor of the preclinical work is high, but it tells us about ERR pharmacology and about effects in mice — not about safety, dosing, or efficacy in humans. No human clinical trials have been performed. The compound is sold by research-chemical suppliers for laboratory use only and is not authorized for human use in any jurisdiction.
Myth
SLU-PP-332 is undetectable in anti-doping testing because it is so new.
Reality
Two papers published in 2026 in mass spectrometry journals specifically characterized SLU-PP-332 and SLU-PP-915 metabolites for doping-control detection. Anti-doping laboratories are actively developing the assays, and routine testing for these compounds is a near-term reality. Athletes who use SLU-PP-332 expecting to evade detection are likely to be wrong on a short time horizon.
Published Research
8 studiesChemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling.
In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential.
An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity.
Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study.
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.
A Synthetic ERR Agonist Alleviates Metabolic Syndrome.
Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney.
Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity.
The foundational 2023 ACS Chemical Biology paper from the Burris lab. Established SLU-PP-332 as a pan-ERR agonist that reproduces the aerobic-exercise transcriptional program in mouse muscle and enhances treadmill endurance — the 'exercise mimetic' origin paper.
Quick Facts
- Class
- Exercise Mimetic
- Tier
- D
- Evidence
- Preliminary
- Safety
- Limited Data
- Updated
- Apr 2026
- Citations
- 8PubMed
Also known as
Tags
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.