SLU-PP-332 250mcg – 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 landmark 2023 Nature 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, Nature), 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].

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. Nat Commun. 2023;14:6938.
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.
3. Xu W, Billon C, Li H, et al. Novel pan-ERR agonists ameliorate heart failure through enhancing cardiac fatty acid metabolism. Circulation. 2024;149:227–250.