SLU-PP-332 — what the research says about the ERR agonist and “exercise mimetic”

In October 2024 the journal Nature Metabolism published a paper that triggered a wave of headlines about an “exercise pill”. Burris’s team at Saint Louis University showed that the small organic molecule SLU-PP-332 — a pan-agonist of ERR receptors — increased running time to exhaustion in mice by roughly 70%, without physical training. The biohacker community treated this data as a prophecy of a new generation of “exercise mimetics”. The academic community treated it exactly as it should: as an interesting signal from an animal model that requires rigorous replication and — most importantly — has never been tested in humans. In the One Peptides catalogue the molecule is available as SLU-PP-332 500 mcg.

SLU-PP-332 is a small organic molecule from the ERR pan-agonist class (Estrogen-Related Receptors α/β/γ), developed in Thomas Burris’s laboratory at Saint Louis University. Studied in mouse models as an “exercise mimetic” candidate. No registration as a medicine, zero clinical data in humans, Research Use Only status.

Regulatory note — a critical distinction

SLU-PP-332 functions solely as a research reagent (Research Use Only). The molecule is not a registered medicine, holds no EFSA authorisation and has never been tested in human clinical trials. Several “exercise mimetics” — AICAR, MOTS-c and GW501516 — are named on the WADA Prohibited List (section S4.4.1).

What SLU-PP-332 is — origin and pharmacological class

The name SLU-PP-332 is an institutional acronym: Saint Louis University, Pharmaceutical Probe 332. The molecule was designed and synthesised in the laboratory of Thomas Burris, one of the world’s leading specialists in nuclear receptor pharmacology. For more than two decades Burris has published work on ERR, REV-ERB, PPAR and related transcription factors regulating mitochondrial metabolism.

Chemical characteristics

What ERR receptors are — Estrogen-Related Receptors

ERR (Estrogen-Related Receptors) are a family of nuclear receptors discovered in 1988 by Vincent Giguère. The family comprises three isoforms: ERRα (dominant in tissues with high energy demand), ERRβ (embryonic development and CNS), ERRγ (skeletal muscle and cardiac muscle).

The name “estrogen-related” is misleading. ERRs were classified as “estrogen-related” solely because of their amino acid sequence similarity to the estrogen receptor (ERα). In reality, ERRs do not bind estradiol. Receptor activity is regulated mainly by transcriptional coactivators, in particular PGC-1α.

Biological functions of ERR

• Mitochondrial biogenesis — co-regulation with PGC-1α
• Expression of oxidative phosphorylation genes
• Fatty acid metabolism — regulation of β-oxidation in muscle
• Modulation of muscle fibre type — shifting the profile towards type I fibres (oxidative, endurance)
• Response to endurance training

Mechanism — an “exercise” metabolic programme without exercise

SLU-PP-332 binds to the ligand pocket of all three ERR isoforms (hence “pan-agonist”). The consequences observed in mouse models:

• Increased expression of mitochondrial genes in skeletal muscle
• Enhanced mitochondrial biogenesis
• Increased fatty acid oxidation
• Shifting of the fibre profile towards type I (slow-twitch)
• Partial replication of the metabolic phenotype of endurance training — in a mouse model

That last point is of fundamental importance. The ERR mechanism activates one axis among the many components of the body’s response to physical exercise. Endurance training acts in parallel on the cardiovascular system, the skeletal system, the central nervous system and hormonal balance. Pharmacological activation of ERR receptors replicates a fragment of the metabolic programme — and nothing beyond that.

The Burris lab 2024 publication — what was actually shown

In 2024 the team of Billon et al. published a paper presenting a series of experiments in mouse models on the pharmacological effects of SLU-PP-332.

Key findings of the publication

What this data actually means

The academic interpretation requires considerably more cautious language:

This is mouse data, not human data. Mouse models have a fundamentally different metabolism — faster energy turnover, shorter life cycles, a different cardiovascular physiology.

Replication in other laboratories remains ongoing. A single publication — even in a journal of this calibre — does not constitute scientific proof.

Long-term safety has not been characterised. Four weeks of administration in mice is a very short time horizon. ERR receptors regulate cardiac muscle metabolism — long-term pharmacological activation of this axis in large populations has not been studied.

No phase I clinical trials in humans. SLU-PP-332 has not undergone any safety study in healthy volunteers.

“Exercise mimetic” — what the class is and why it does not replace training

Representative molecules of the class

What a single molecule does not reproduce

• Cardiovascular system: concentric left ventricular hypertrophy, increased stroke volume
• Skeletal system: mechanical loading stimulates bone remodelling
• Central nervous system: increased BDNF, improved cognitive function
• Immune system: modulation of the cytokine profile
• Gut microbiome: changes in microbiota composition
• Structural adaptations of connective tissue: strengthening of tendons and ligaments

Regulatory and WADA status

Medicine: SLU-PP-332 holds no registration in any jurisdiction worldwide.

Food supplement: SLU-PP-332 holds no EFSA authorisation. Full context on its legal status in the article on EU law. Any promotion of SLU-PP-332 as a performance supplement constitutes a breach of EU food law.

WADA status

Several “exercise mimetics” are named on the 2026 WADA Prohibited List: AICAR, MOTS-c and GW501516 (cardarine), in section S4.4.1 (metabolic modulators). They are prohibited at all times, in and out of competition. Athletes subject to the WADA Code are obliged to verify the current guidelines before any contact with research reagents from this class.

SLU-PP-332 as a research reagent

The One Peptides catalogue offers SLU-PP-332 in 500 mcg powder form. Standards: HPLC ≥98%, MS, COA per batch, cold chain. A full description of the QA process is on the quality testing and certificates page.

Frequently asked questions

Does SLU-PP-332 replace exercise in humans?

No. All published data come from mouse models. SLU-PP-332 has never been tested in human clinical trials. A single molecule acting on ERR receptors replicates a fragment of the skeletal muscle metabolic programme in an animal model, but does not reproduce the full spectrum of systemic adaptation.

SLU-PP-332 and weight loss?

In mouse models a reduction in adipose tissue mass was observed (Billon et al. 2024). No clinical trials in humans — any extrapolations remain hypothetical. The molecule remains solely a Research Use Only research reagent.

What does “exercise mimetic” mean?

“Exercise mimetic” is a descriptive term denoting molecules that partially replicate the biochemical phenotype of physical exercise in laboratory models. Representative examples are AICAR, GW501516 (cardarine), MOTS-c, and ERR receptor agonists. None of these molecules reproduces the full adaptive programme of the response to training.

Where does the name SLU-PP-332 come from?

SLU — Saint Louis University, PP — Pharmaceutical Probe, 332 — the number in the internal project numbering of Burris’s team.

Is SLU-PP-332 on the WADA list?

SLU-PP-332 is not named on the 2026 WADA Prohibited List. That does not make it permitted: section S0 covers pharmacological substances not addressed by other sections of the List and with no approval for human therapeutic use — and SLU-PP-332 has no such approval. Related metabolic modulators — AICAR, MOTS-c and GW501516 — are named in section S4.4.1. Athletes subject to the WADA Code are obliged to verify the current guidelines.

Related content in the knowledge base

Among compounds studied in relation to non-incretin metabolic pathways, we also describe: BAM-15 (a mitochondrial uncoupler), 5-amino-1MQ (an NNMT inhibitor) and Tesofensine (a triple monoamine reuptake inhibitor).

The conceptually strongest analogy to SLU-PP-332 remains MOTS-c — a mitochondrial peptide described in the context of exercise mimetics. The two compounds share the idea of pharmacological modulation of the mitochondrial programme, although they act at entirely different levels of regulation.

The contrast with the incretins highlights a fundamental difference in pharmacological routes: incretins — semaglutide, tirzepatide, retatrutide — modify gastrointestinal physiology, whereas SLU-PP-332 modifies the transcriptional programme of muscle. A full overview in the guide to GLP-1 peptides.

Summary

SLU-PP-332 is an interesting research reagent at a very early stage of preclinical development. The publication by Billon et al. (2024) showed in a mouse model that the ERR receptor pan-agonist increases running endurance by roughly 70% without training, reduces adipose tissue mass and improves the lipid profile.

The public hype about an “exercise pill” remains, however, considerably ahead of the scientific reality. Mouse data are not human data. The absence of phase I trials means no characterised pharmacokinetics, no adverse-effect profile and no efficacy confirmed in a human population. Physical training remains irreplaceable.

Final disclaimer — Research Use Only

SLU-PP-332 is a research reagent (Research Use Only) with no registration as a medicine and no EFSA authorisation as a food supplement ingredient. All published data come from mouse models or in vitro tests. Several compounds of this class — AICAR, MOTS-c and GW501516 — are on the WADA Prohibited List (section S4.4.1). Not for human administration. Not intended for consumption.

Bibliography

1. Billon C et al. (2024). A Synthetic ERR Agonist Alleviates Metabolic Syndrome
2. Wei W et al. (2023). Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity
3. Audet-Walsh É, Giguère V (2015). The multiple universes of estrogen-related receptor α and γ in metabolic control
4. Fan W, Evans R (2015). PPARs and ERRs: molecular mediators of mitochondrial metabolism

Bartosz BartczakPhysiotherapist, Personal Trainer

Physiotherapist with 20 years of clinical experience, graduate of Poznan University of Medical Sciences. Founder of One Peptides and lead author of clinical-perspective content.

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