SLU-PP-332

SLU-PP-332 (CAS 2226909-79-9; molecular formula C25H26N2O5S; molecular weight 466.55) is a small-molecule pan-agonist of the estrogen-related receptor (ERR) family of orphan nuclear receptors developed at the Saint Louis University School of Medicine by Thomas Burris and colleagues. The ERR family comprises three isoforms (ERRalpha, ERRbeta, ERRgamma) that share substantial sequence homology with the estrogen receptor but bind distinct ligands and target distinct gene programs; the principal ERR-regulated gene programs include mitochondrial biogenesis, fatty acid oxidation, oxidative phosphorylation, and skeletal muscle oxidative fiber phenotype. ERR activity is induced by exercise and is one of the principal transcriptional drivers of the exercise-induced metabolic adaptation phenotype, alongside PGC-1alpha (which is itself an ERR coactivator). SLU-PP-332 was characterized as an inverse partial agonist or full agonist depending on the assay, with similar potency at all three ERR isoforms (EC50 in the low-nanomolar to mid-nanomolar range). Reported in vivo effects in rodent models include increased exercise endurance (treadmill running time approximately doubled in mice receiving the compound at 50 mg/kg subcutaneous daily for several weeks without exercise training), elevation of mitochondrial gene expression in skeletal muscle, reduction of body fat mass on high-fat diet, and protection against age-related muscle dysfunction. The pharmacological profile has motivated interest in the compound as an exercise mimetic for metabolic and aging indications. The compound is research-grade and not approved by any regulatory authority; clinical development through partner companies has been announced but no Phase 1 readouts have been published as of the most recent monograph revision. Reconstitution requires DMSO or co-solvent owing to limited aqueous solubility; storage of solid material at refrigerated or frozen conditions.