SLU-PP-915

Overview

SLU-PP-915 is a synthetic small-molecule pan-agonist of the estrogen-related receptors (ERRα, ERRβ, ERRγ) — it is not a peptide. Developed at Saint Louis University and the University of Florida, it is described as the first orally bioavailable pan-ERR agonist and is studied preclinically as an "exercise mimetic" targeting oxidative metabolism. It is a research chemical, not approved by the FDA or any regulator, and has no published human trials — all efficacy data come from rodent models.

Mechanism of Action

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).

Research Summary

SLU-PP-915 is a second-generation analog of the prototype ERR agonist SLU-PP-332. In a Journal of Pharmacology and Experimental Therapeutics study (Billon et al.), orally administered SLU-PP-915 increased aerobic exercise capacity — running distance and duration — in mice to an extent comparable to intraperitoneal SLU-PP-332 after adjusting for systemic exposure, and induced ERR target genes in muscle. The authors position orally active ERR agonists as candidate agents for metabolic disorders (obesity, type 2 diabetes, metabolic-dysfunction-associated steatohepatitis), cardiovascular disease (heart failure), and muscle pathologies (sarcopenia, muscular dystrophies). Separate analytical work (Möller et al., Rapid Communications in Mass Spectrometry, 2026) characterized the in-vitro metabolism of SLU-PP-332 and SLU-PP-915 and flagged both as compounds with doping potential, anticipating misuse as exercise mimetics. As of 2026 there are no human clinical trials of SLU-PP-915; all efficacy evidence is preclinical.

Dosing Information

Reported Side Effects

• No controlled human safety data — SLU-PP-915 has never been tested in humans
• Off-target and long-term effects unknown
• Systemic consequences of chronic pan-ERR agonism in humans are uncharacterized
• Contains a boronic-acid moiety whose human toxicology in this context is unstudied

Research References

• An orally active estrogen receptor–related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity (2025)
• In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential (2026)
• Slu-PP-915 — PubChem Compound Summary (CID 142532359) (2026)