SLU-PP-332

SLU-PP-332 is an agonist of estrogen-related receptor α (ERRα), ERRβ, and ERRγ.¹ It induces reporter gene expression in HEK293 cells expressing ERRα, ERRβ, or ERRγ (EC₅₀s = 98, 230, and 430 nM, respectively). SLU-PP-332 (10 µM) increases mitochondrial respiration in C2C12 skeletal myoblasts. It increases the number of quadricep oxidative muscle fibers and quadricep cytochrome C, myosin IIA, and mitochondrial DNA (mtDNA) levels, as well as increases running distance, length of time running, and grip strength, in mice when administered at a dose of 50 mg/kg twice per day. SLU-PP-332 (25 mg/kg per day for eight weeks) inhibits age-related increases in albuminuria and kidney weights and age-related decreases in kidney podocin levels in a mouse model of age-related kidney dysfunction.² It decreases body weight and fat mass, blood levels of total cholesterol, HDL, and triglycerides, and adipocyte size in a mouse model of high-fat diet-induced obesity when administered at a dose of 50 mg/kg twice per day.³ It reduces blood glucose levels in a glucose tolerance test in the same animals at the same dose.

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1. Billon, C., Sitaula, S., Banerjee, S., et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem. Biol. 18(4), 756-771 (2023).

2. Wang, X.X., Myakala, K., Libby, A.B., et al. Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney. Am. J. Pathol. 193(12), 1969-1987 (2023).

3. Billon, C., Schoepke, E., Avdagic, A., et al. A synthetic ERR agonist alleviates metabolic syndrome. J. Pharmacol. Exp. Ther. 388(2), 232-240 (2024).