SLU-PP-332 250 mcg – 60 capsules

SLU-PP-332 250 mcg — 60 research capsules in a glass bottle. SLU-PP-332 is the first orally bioavailable, pan-ERR (estrogen-related receptor) agonist — and arguably the most striking exercise-mimetic compound to emerge from academic medicinal chemistry in the past decade. In a 2023 ACS Chemical Biology paper from the Burris group, oral SLU-PP-332 increased running endurance by ~70 % in mice, reprogrammed skeletal muscle toward an oxidative, type-IIa-rich phenotype, and produced these adaptations without acting on the central nervous system or altering food intake. It has rapidly become the reference tool compound for studying the transcriptional layer of training adaptation.

Research Overview

SLU-PP-332 is a small-molecule pan-agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ), a family of orphan nuclear receptors that sit at the master-regulator level of mitochondrial biogenesis, oxidative phosphorylation and fatty-acid utilization [1]. Unlike caffeine, β-agonists or thyroid analogues, SLU-PP-332 carries no central stimulant activity and does not modulate appetite — it works exclusively through transcriptional reprogramming of metabolic gene expression in skeletal muscle, heart and adipose tissue [1,2]. In Billon et al. (2023, ACS Chem Biol), four weeks of oral dosing in mice increased treadmill running distance by ~70 %, expanded type-IIa oxidative fibers, and elevated mitochondrial content even in sedentary animals [1]. Subsequent work has demonstrated activity against diet-induced obesity, hepatic steatosis and heart-failure models, positioning SLU-PP-332 as the lead chemical probe for the entire ERR-PGC-1α axis [2,3].

Primary Research Areas

• ERRα / ERRβ / ERRγ pharmacology: the only well-characterized small molecule that engages all three ERR isoforms in a physiologically meaningful dose range, enabling clean dissection of nuclear-receptor-driven transcription [1].
• Mitochondrial biogenesis and oxidative capacity: used to probe PGC-1α-coordinated upregulation of TCA-cycle enzymes, electron-transport-chain components and fatty-acid β-oxidation machinery in skeletal muscle and cardiomyocytes [1,2].
• Exercise-mimetic phenotypes: the reference tool for studying transcriptional adaptations of endurance training in sedentary models, including fiber-type shifting toward oxidative type-IIa [1].
• Metabolic disease models: investigated in diet-induced obesity, hepatic steatosis, and insulin-resistance paradigms where it improves systemic substrate utilization without weight loss in lean animals [2].
• Cardiac energetics and heart failure: evaluated in rodent models of pressure-overload and ischemia-reperfusion, where ERR activation rescues cardiac mitochondrial gene expression and contractile reserve [3].
• Endurance without training: in sedentary mice, seven days of treatment increased running time to exhaustion by about 70% and distance by about 45%, with more oxidative (type IIa) muscle fibers and more mitochondria; two weeks also increased grip strength. The catch is that it was injected, not swallowed: the same group later reported that SLU-PP-332 is not orally bioavailable and built SLU-PP-915 for the oral route, which matters for a capsule [1,4].
• Fat and insulin: in obese mice it raised energy expenditure and fat burning, reduced fat mass and improved insulin sensitivity [2].
• Heart: in mice with pressure-overload heart failure, ERR agonists improved the pumping function and reduced fibrosis by restoring the heart’s ability to burn fat. Relevant to heart failure, where the failing heart loses the ability to use fat as fuel [3].
• Aging kidney: in 21-month-old mice, eight weeks of treatment reversed protein loss in the urine, the loss of podocytes, mitochondrial dysfunction and inflammation – an effect comparable to lifelong calorie restriction. Kidney function declines with age in everyone, which is what makes this interesting beyond the model [5].
• Human muscle cells: in muscle cells taken during hip surgery from physically inactive women, SLU-PP-332 raised SIRT1, PGC-1α, ERRα and irisin (FNDC5), lowered oxidative stress and cell senescence, and helped the cells form muscle fibers. This is the closest thing to human data so far [6].

References

1. Billon C, Sitaula S, Banerjee S, 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
2. Billon C, Schoepke E, Avdagic A, 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
3. Xu W, Billon C, Li H, 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
4. Billon C, Appourchaux K, Côté I, et al. 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
5. Wang XX, Myakala K, Libby AE, 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
6. Bonanni R, Falvino A, Matticari A, 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