SLU-PP-332 (also referenced as SLU-PP-322) is a synthetic small molecule agonist of the estrogen-related receptor alpha and gamma (ERRα/γ) — nuclear receptors that govern mitochondrial biogenesis, oxidative metabolism, and skeletal muscle fiber-type determination. Published research shows SLU-PP-332 activates the same gene expression programs induced by aerobic exercise, making it a highly studied exercise mimetic research tool.
ERRα/ERRγ agonist | Small molecule exercise mimeticBinds and activates estrogen-related receptors α and γ in mitochondria and nucleus, triggering PGC-1α-dependent gene programs.
Upregulates TFAM, NRF1, and oxidative phosphorylation genes — expanding mitochondrial density in treated muscle tissue.
Promotes Type I (slow, oxidative) fiber gene expression in skeletal muscle, increasing endurance capacity without training.
Mice treated with SLU-PP-332 showed improved cardiac function and reduced obesity-related cardiac remodeling in diet-induced obesity models.
Kamber et al. (Washington University, 2023) demonstrated SLU-PP-332 activated ERR-regulated oxidative metabolism genes in mice, increased VO₂max-equivalent capacity, and protected from obesity-induced metabolic dysfunction without exercise.
J Med Chem. 2023;66(16):11137–11168Treatment with SLU-PP-332 improved ejection fraction and reduced cardiac fibrosis in murine heart failure models by restoring mitochondrial biogenesis gene programs lost in diseased tissue.
Circulation. 2024;149(12):949–962Obese mice treated with SLU-PP-332 showed reduced adiposity, improved glucose tolerance, and restored mitochondrial function in skeletal muscle — all without dietary restriction.
J Med Chem. 2023;66(16):11137–11168Published murine studies: 30 mg/kg SC or IP daily. In vitro muscle cell studies: 1–30 µM. Endpoints: ERR target gene expression (qPCR: ACADM, COX4, TFAM), mitochondrial content (Mitotracker, citrate synthase activity), oxygen consumption rate (Seahorse), and treadmill/wheel running capacity.
| Type | Small molecule ERRα/γ nuclear receptor agonist |
| Target | ERRα and ERRγ (nuclear receptors) |
| Mechanism | Exercise mimetic via PGC-1α/mitochondrial biogenesis |
| Purity | ≥99% by HPLC |
| Appearance | White/off-white crystalline powder |
| Storage | −20°C, desiccated, DMSO stock stable |
