Description
SLU-PP-332 is a small-molecule synthetic compound classified as a pan-agonist of the estrogen-related receptors (ERRs), a subfamily of orphan nuclear receptors that includes the ERRα, ERRβ, and ERRγ subtypes. Among the three subtypes, SLU-PP-332 exhibits its greatest potency at ERRα, with a reported EC50 of 98 nM [5]. The compound emerged from structure-based design efforts aimed at producing an ERR-targeting tool with pharmacokinetic properties suitable for use in preclinical in vivo models, a profile that had previously been difficult to achieve for ERRα-selective agents in particular [2].
From a structural standpoint, SLU-PP-332 is distinct from endogenous steroid ligands and represents a fully synthetic chemotype capable of engaging all three ERR isoforms simultaneously [2][3]. This pan-ERR activity profile distinguishes it from earlier ERRβ/γ-selective agonists and has made it a valuable chemical probe for dissecting the individual and overlapping contributions of each receptor subtype to downstream transcriptional programs.
Researchers have employed SLU-PP-332 principally to investigate the biology of ERR-driven metabolic regulation. Studies in cell and animal models have used the compound to interrogate mechanisms governing mitochondrial bioenergetics, fatty acid oxidation, and oxidative skeletal muscle fiber remodeling [2][3]. Additional preclinical investigations have explored its utility as a molecular tool for studying metabolic syndrome [1], cardiac energy metabolism [3], and age-associated renal mitochondrial dysfunction and inflammation [4].
References
[1] A Synthetic ERR Agonist Alleviates Metabolic Syndrome. The Journal of Pharmacology and Experimental Therapeutics, 2024. https://pubmed.ncbi.nlm.nih.gov/37739806/
[2] Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chemical Biology, 2023. https://pubmed.ncbi.nlm.nih.gov/36988910/
[3] Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation, 2024. https://pubmed.ncbi.nlm.nih.gov/37961903/
[4] Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney. The American Journal of Pathology, 2023. https://pubmed.ncbi.nlm.nih.gov/37717940/
[5] SLU-PP-332. Wikipedia. https://en.wikipedia.org/wiki/SLU-PP-332
