SLU-PP-332

Functions as a potent, synthetic pan-agonist of the Estrogen-Related Receptors (ERRα, ERRβ, ERRγ), with highest affinity for ERRα (EC50 ≈ 98 nM). Unlike standard hormones, it does not bind to estrogen receptors (ERs) but specifically targets the 'orphan' nuclear receptors that control mitochondrial bioenergetics. Mechanistically, it acts as a transcriptional switch that mimics the molecular signals of endurance exercise. Upon binding, it recruits the PGC-1α coactivator complex to specific DNA promoters, triggering a massive upregulation of genes involved in mitochondrial biogenesis, fatty acid oxidation (fat burning), and oxidative phosphorylation (ATP production). In skeletal muscle, it induces a fiber-type switch toward oxidative (Type IIa) fibers—effectively 'training' the muscle tissue without physical exertion. This leads to increased endurance capacity and a systemic shift in metabolism that favors using fat for fuel over glucose, correcting metabolic inflexibility associated with obesity and aging.