SLU-PP-332: Pan-ERR Agonist Functioning as an Exercise Mimetic
SLU-PP-332 is a pre-clinical pan-ERR agonist that simulates the skeletal muscle and mitochondrial adaptations of aerobic exercise, acting as an "exercise mimetic".
Structural Parameters of SLU-PP-332
| Property | Value and Specification | References |
|---|---|---|
| CAS Number | 303760-60-3 | |
| Molecular Formula | C18H14N2O2 | |
| Molecular Weight | 290.32 g/mol | |
| Chemical Structure | Small-molecule hydrazone derivative | |
| Target Receptors | Pan-agonist of Estrogen-Related Receptors (ERRα/β/γ) |
Origin, History, and Research Stage
SLU-PP-332 was synthesized in 2022 by a team led by Thomas Burris at the University of Health Sciences and Pharmacy in St. Louis and Washington University. The compound was developed to study Estrogen-Related Receptors (ERRs) in vivo, which were previously considered difficult to target pharmacologically. Published in 2023, it is currently in pre-clinical development for metabolic syndrome, obesity, and cardiac function.
Mechanism of Action and Pharmacokinetics
SLU-PP-332 acts as a pan-agonist across all three ERR isoforms (ERRalpha, ERRbeta, and ERRgamma), with slightly higher potency at ERRalpha. These receptors regulate transcriptional networks governing mitochondrial function, oxidative phosphorylation, and lipid metabolism. In vivo, SLU-PP-332 activates over 120 metabolic genes, upregulating those involved in fatty acid beta-oxidation, cellular lipid transport, and mitochondrial respiratory chain complexes within skeletal muscle and cardiomyocytes. This broad activation mimics the metabolic adaptations typically induced by chronic aerobic exercise.
Scientific and Clinical Effects
In diet-induced obesity (DIO) mice, SLU-PP-332 reduces adipose tissue accumulation, increases fatty acid oxidation, and lowers circulating triglycerides. In performance models, it doubles running endurance on treadmills by enhancing skeletal muscle oxidative capacity. Additionally, in transaortic constriction (TAC) mouse models of heart failure, SLU-PP-332 limits myocardial fibrosis and preserves ejection fraction, demonstrating cardioprotective efficacy.