Mechanism of Action
SLU-PP-915 is a pan-ERRα/β/γ agonist (EC₅₀ ≈414/435/378 nM), chemically distinct from SLU-PP-332: instead of an acylhydrazide scaffold, it carries a disubstituted thiophene bearing a boronic acid. It was obtained by replacing the hydrazide moiety of GSK-4716 with thiophene rings; substituting the phenolic and aniline groups with a boronic acid preserved receptor binding while substantially improving oral bioavailability (Hampton et al., 2023, Eur J Med Chem) — the main advance is pharmacokinetic, not potency (per-isoform EC₅₀ is somewhat higher, i.e. weaker, than SLU-PP-332's).
Preclinical Data
Hampton, Sitaula, Billon et al. (2025, J Pharmacol Exp Ther): the first orally active pan-ERR agonist; enhances aerobic exercise performance (running distance and duration) comparably to SLU-PP-332 whether given intraperitoneally or orally (adjusted for systemic exposure), and synergizes with exercise training to further boost Ddit4 and mitochondrial gene expression. A related line of work describes pan-ERR agonists of this class in heart failure models, improving cardiac fatty acid metabolism and mitochondrial function (Xu et al., 2023, Circulation). Developed at Saint Louis University and the University of Florida; proposed research applications include metabolic disorders (obesity, T2D, MASH), cardiovascular models, and muscle pathologies (sarcopenia, muscular dystrophies).
Storage
Store in a freezer, airtight container, protect from light and moisture — boronic acids are moisture-sensitive (slow protodeboronation/oxidation).
BIOLABCHEMICALS