SLU-PP-332 vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

SLU-PP-332 activates all three ERR isoforms (α, β, γ) with a modest potency preference for ERRα — orphan nuclear receptors that regulate oxidative metabolism gene programs. Activation drives PGC-1α co-activator pathways, mitochondrial biogenesis (TFAM, NRF1), fatty acid oxidation (CPT1B, ACADM), and a shift toward oxidative type IIa muscle fibers. Note: despite the ERR name, these receptors do not bind estrogen.

The estrogen-related receptors (ERRα/β/γ) are orphan nuclear receptors that act as master transcriptional regulators of oxidative metabolism, driving mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and the TCA cycle — largely as partners of the PGC-1 coactivators. SLU-PP-915 binds and activates all three ERR isoforms with an EC50 of roughly 400 nM at each. In its medicinal-chemistry design, the phenol and aniline groups of earlier ERR agonists were replaced with a boronic-acid moiety on a disubstituted thiophene scaffold, which preserved receptor activity while improving microsomal metabolic stability and oral exposure. In cells and in rodents it upregulates canonical ERR target genes including PGC-1α, lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 4 (PDK4), and DNA-damage-inducible transcript 4 (DDIT4).

Not established in humans; engineered for improved metabolic stability and oral exposure relative to first-generation ERR agonists