Mechanism of Action
ERRs (estrogen-related receptors) are orphan nuclear receptors — despite the name, they are not regulated by estrogen. SLU-PP-332 is a non-selective pan-agonist of all three isoforms, with the highest affinity for ERRα (EC₅₀ = 98 nM; ERRβ 230 nM, ERRγ 430 nM). ERRα activation triggers the transcriptional program for mitochondrial biogenesis and fatty acid oxidation — the same program switched on by acute aerobic exercise (hence the "exercise mimetic" label); the in vitro effect has been shown in skeletal muscle cell lines (increased mitochondrial respiration).
Preclinical Data
Billon et al. (2023, ACS Chem Biol): in mice, SLU-PP-332 ERRα-dependently reproduces the acute genetic response to aerobic exercise and increases exercise capacity (running time/distance). Billon et al. (2024, J Pharmacol Exp Ther): in diet-induced obese and genetically obese (ob/ob) mice — increased energy expenditure and fatty acid oxidation, reduced fat mass (~25-30% over 28 days without exercise), improved insulin sensitivity and glucose tolerance, with no change in food intake.
Fresh Data (2025)
Frontiers in Physiology (2025, pilot study): primary myoblasts derived from muscle biopsies of 20 elderly women (active/sedentary). In cells from sedentary donors, SLU-PP-332 lowered NOX4 and raised SIRT1, PGC-1α, ERRα, FNDC5, Akt, and Bcl-2, reducing oxidative stress, cytotoxicity, and cellular senescence, and promoted myotube formation.
Important Limitation
SLU-PP-332 has poor oral bioavailability — a significant pharmacokinetic drawback. This is why the Burris lab developed the successor compound SLU-PP-915 with improved oral activity (Hampton et al., 2023, Eur J Med Chem).
Storage
White to off-white powder, insoluble in water (soluble in DMSO, ~29 mg/mL). Store in a freezer, airtight container, protect from light and moisture.
BIOLABCHEMICALS