Endurance exercise changes which genes muscle cells use. SLU-PP-332 is studied because it activates a set of receptors involved in that switch.
SLU-PP-332 · Oestrogen-related receptor agonist
When muscle is trained, its cells turn on genes that build more mitochondria and burn more fat. Part of that programme is controlled by the oestrogen-related receptors, proteins that sit on DNA and regulate metabolic genes. SLU-PP-332 is a synthetic molecule that activates them, and researchers use it to ask which parts of the exercise response those receptors control. The evidence is from cells and mice.
SLU-PP-332 is a small synthetic molecule, not a peptide, first reported in 2023 by a group at Saint Louis University and the St. Louis College of Pharmacy. It is an agonist, a molecule that activates a receptor, of all three oestrogen-related receptors (ERRα, ERRβ and ERRγ), with the highest potency at ERRα (Billon et al. 2023).
Despite the name, oestrogen-related receptors do not bind oestrogen. They are nuclear receptors, proteins that sit on DNA and switch genes on or off, and they regulate genes for mitochondrial biogenesis (making new mitochondria) and oxidative metabolism (burning fat and sugar with oxygen) in muscle and heart. Genetic studies had linked them to exercise capacity, but chemical tools that activate ERRα in a living animal were lacking. SLU-PP-332 was made to fill that gap, which is why it is described in the literature as an 'exercise mimetic': a compound that triggers some of the gene changes exercise produces.
In a mouse skeletal-muscle cell line, SLU-PP-332 increased mitochondrial function and cellular respiration. In mice, treatment increased the proportion of type IIa oxidative muscle fibres, the fatigue-resistant fibres favoured by endurance training, and lengthened running time to exhaustion; the acute gene response depended on ERRα (Billon et al. 2023, ACS Chemical Biology). A follow-up in diet-induced obese and ob/ob mice reported higher energy expenditure and fatty-acid oxidation, less fat gain and improved insulin sensitivity; it appeared online in September 2023 and in print in the Journal of Pharmacology and Experimental Therapeutics in January 2024 (Billon et al. 2024).
A separate collaboration led from Baylor College of Medicine examined SLU-PP-332 and a second pan-ERR agonist, SLU-PP-915, in a mouse model of pressure-overload heart failure. Both improved ejection fraction, reduced fibrosis and increased survival, with ERRγ identified as the main mediator in heart; the paper appeared online in November 2023 and in Circulation in January 2024 (Xu et al. 2024).
No human study of SLU-PP-332 has been published.
Everything known comes from cells and mice over weeks, not from people. Activating a gene programme is not the same as exercising: the compound does not reproduce the mechanical, cardiovascular or behavioural effects of training, and the papers do not claim it replaces exercise or extends lifespan.
Mouse endurance and metabolic findings do not establish the same effect in humans, and the relevant ERR subtype differs by tissue (ERRα in muscle, ERRγ in heart), so results in one organ do not transfer to another. Safety, pharmacokinetics and long-term exposure in humans are undescribed. Several authors hold interests in companies developing ERR-based therapeutics, which the papers disclose.
SLU-PP-332 is not an approved medicine in Australia (no ARTG entry identified) and has no marketing approval identified elsewhere; it is a preclinical research compound.
Sources and status checked 2026-09-22
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