Amlexanox vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

Two distinct mechanisms are documented. For its approved aphthous-ulcer indication, in vitro studies show amlexanox inhibits formation and release of inflammatory mediators (histamine, leukotrienes) from mast cells, neutrophils, and mononuclear cells, though the FDA label states the mechanism of ulcer healing is unknown. In preclinical metabolic research, amlexanox was identified as a selective ATP-competitive inhibitor of the non-canonical IκB kinases TBK1 and IKKε, which suppresses chronic low-grade inflammatory signaling implicated in obesity-linked insulin resistance.

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).

No validated human dose for metabolic or research use

No human dose established