SLU-PP-332 — “Exercise in a Capsule” (Synthetic Pan-ERR Agonist)
1. Molecular Identity & Mechanism
•Pan‑ERR Activation – SLU‑PP‑332 is a potent, balanced agonist of the estrogen‑related receptors (ERRα, ERRβ, ERRγ), with strongest affinity for ERRα (EC₅₀ ≈ 98 nM) .
•Mitochondrial & Metabolic Cascade – Activates mitochondrial biogenesis, oxidative phosphorylation (OXPHOS), fatty acid β-oxidation, and thermogenesis by triggering genes like PGC‑1α, GLUT4, TFAM, CPT1, UCPs, and AMPK pathways .
2. Exercise-Mimetic & Endurance Boost
•Replicates aerobic exercise benefits—improves endurance, enhances skeletal muscle mitochondrial density, increases oxidative (Type IIa) muscle fibers and capillarization .
•In mice, led to greater running capacity and a “trained” metabolic phenotype without physical training .
3. Metabolic Health & Fat Loss
•Fat Reduction – In diet‑induced obese mice, it reduced fat mass gain (~12% weight loss), decreased adipocyte size, and lowered hepatic steatosis .
•Improved Lipid Profile – Lower total cholesterol, triglycerides, and fasting insulin levels; improved glucose tolerance, especially on high‑fat diets  .
•Unchanged Appetite – Weight and metabolic improvements occurred without altering food intake  .
4. Anti-Aging, Mitochondrial & Organ Protection
•Enhances Cellular Energy – Restores mitochondrial respiration in aged or diseased tissues (kidney, heart, liver), supports autophagy/mitophagy, and reduces age‑related inflammation and fibrosis .
•Cardioprotective Effects – In preclinical models, it preserved contractility, reduced cardiomyocyte apoptosis, and limited pathological remodeling .
•Anti‑Inflammatory Action – Suppresses inflammatory markers like IL‑6 and TNF‑α and reduces oxidative tissue damage .
5. Potential Broader Applications
•Metabolic Disorders – Promise in addressing obesity, type 2 diabetes, metabolic syndrome, NAFLD, and insulin resistance .
•Renal, Cardiac, Cognitive Support – May offer kidney protection, improve post‑ischemic recovery, and support neurodegenerative conditions via mitochondrial and anti‑inflammatory mechanisms   .
•Longevity Research – Investigated for its potential to extend healthspan, via enhancing mitochondrial and metabolic resilience .
