SLU-PP-332 (Exercise Mimetic): Research, Mechanism & Current Evidence
Experimental compound studied as an exercise mimetic in mice. Not a peptide; no human data exists.
Also known as pan-ERR agonist · estrogen-related receptor agonist · Exercise Mimetic
What is SLU-PP-332?
SLU-PP-332 is a small synthetic molecule, not a peptide, developed at Saint Louis University in the laboratory of Thomas Burris. The name comes from the institution.
It is very early-stage. Published work is confined to cell and mouse studies, and it has never been given to humans in a published trial.
Status: Preclinical. No human studies published.
What is SLU-PP-332 researched for?
Its label as an exercise mimetic comes from the observation that it switches on some of the same genetic programmes that endurance exercise activates in muscle.
Studied endpoints in mice include fat mass, exercise capacity, and markers of mitochondrial density in muscle tissue.
- Significantly improved glucose tolerance in obese mice with lower fasting glucose and insulin levels.
- Increases resting energy expenditure by 25% for fatty acid oxidation within 2 hours.
- Reduced hepatic steatosis, decreased hepatic triglycerides, and enhanced hepatic fatty acid oxidation.
- 70% increase in running time and 45% increase in running distance in preclinical models.
- Increased type IIa oxidative skeletal muscle fibers with enhanced oxidative capacity.
- Improved ejection fraction in heart failure models with reduced cardiac fibrosis.
- First compound to reverse age-related mitochondrial dysfunction in 21-month-old mice.
- Reversed age-related albuminuria increase and prevented podocyte loss in elderly mice.
How does SLU-PP-332 work?
It activates the estrogen-related receptors, a family of proteins — ERRα, ERRβ and ERRγ — that control genes governing how muscle cells produce energy. Despite the name, these receptors are not activated by oestrogen.
Activating them shifts muscle toward the oxidative, endurance-type metabolism that training normally produces.
Reported targets: estrogen-related receptor
What does the research show?
Mouse studies reported reduced fat mass on a high-fat diet and increased running capacity over short study periods, without changes in food intake.
That is the extent of the evidence. There are no human data of any kind.
Limitations of the current evidence
Describing something as an exercise mimetic in a mouse is a statement about gene expression, not a claim that it substitutes for training in people.
Broad nuclear receptor activation raises questions about off-target effects that have not been addressed in long-term studies.
Pharmacokinetics are poor enough that the original compound was reported to require injection, and improved analogues are being developed.
References
A Synthetic ERR Agonist Alleviates Metabolic Syndrome
Billon C, Schoepke E, Avdagic A, et al. · The Journal of pharmacology and experimental therapeutics · 2024
Diet-induced obese mice, 50 mg/kg IP twice daily, 28 days: 12% body weight loss, 25% fatty acid oxidation increase, improved glucose tolerance, reduced hepatic steatosis. SLU-PP-332 mimics exercise-induced metabolic benefits.
Animal study · PMID 37739806
Billon C, Sitaula S, Banerjee S, et al. · ACS chemical biology · 2023
Multiple mouse models, 50 mg/kg IP: 70% increase in running time, 45% increase in running distance, increased type IIa oxidative muscle fibers. SLU-PP-332 is a synthetic ERR pan agonist with highest potency for ERRα.
Animal study · PMID 36988910
Wang XX, Myakala K, Libby AE, et al. · The American journal of pathology · 2023
21-month-old mice, 8-week treatment with SLU-PP-332: Reversed age-related increases in albuminuria, podocyte loss, mitochondrial dysfunction, and inflammatory cytokines.
Animal study · PMID 37717940
Xu W, Billon C, Li H, et al. · Circulation · 2024
Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival in pressure overload-induced heart failure without affecting cardiac hypertrophy. Transcriptionally activated fatty acid metabolism and mitochondrial function genes.
PMID 37961903
Common questions
Why does SLU-PP-332 work so much faster than training (12% weight loss in 28 days)?
Training requires weeks to upregulate mitochondrial genes; SLU-PP-332 activates them within hours. In mouse studies, energy expenditure increased 25% within 2 hours, creating sustained fat oxidation and rapid weight loss. This bypass of normal training adaptation pathways explains the speed, though long-term human data doesn't exist.
Is there an oral version of SLU-PP-332 in development?
Yes. SLU-PP-915 (a distinct oral bioavailable ERR pan-agonist) shows similar efficacy to SLU-PP-332 when given orally. A 2025 study found it enhanced aerobic performance as effectively as the injectable form. This represents major progress toward clinical translation, though human trials haven't started.