SLU-PP-332

SLU-PP-332SLU PP 332 is a synthetic small molecule compound classified as a potent, non selective pan agonist of estrogen related receptors (ERRs), specifically targeting ERR, ERR, and ERR with EC50 values of 98 nM, 230 nM, and 430 nM, respectively, in cell based cotransfection reporter assays. Chemically identified as (E) 4 Hydroxy N (naphthalen 2 ylmethylene)benzohydrazide (CAS No. 303760 60 3, molecular formula C18H14N2O2, molecular weight 290. 32 g mol),

SLU-PP-332 is a synthetic small-molecule compound classified as a potent, non-selective pan-agonist of estrogen-related receptors (ERRs), specifically targeting ERRα, ERRβ, and ERRγ with EC50 values of 98 nM, 230 nM, and 430 nM, respectively, in cell-based cotransfection/reporter assays. Chemically identified as (E)-4-Hydroxy-N′-(naphthalen-2-ylmethylene)benzohydrazide (CAS No. 303760-60-3, molecular formula C18H14N2O2, molecular weight 290.32 g/mol), SLU-PP-332 selectively activates ERRs without engaging classical estrogen receptors (ERα, ERβ), thus avoiding estrogenic side effects.

Developed at Saint Louis University, SLU-PP-332 mimics the metabolic effects of aerobic exercise by enhancing mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation. It activates key metabolic pathways, including AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), while inducing the expression of DDIT4, a regulator of cellular stress response. In preclinical studies, SLU-PP-332 increased mitochondrial respiration in C2C12 myocytes and promoted fast oxidative skeletal muscle fibers (Type IIa) in mice, enhancing exercise endurance in an ERRα-dependent manner.

In mouse models of obesity and metabolic syndrome, SLU-PP-332 (50 mg/kg, intraperitoneal, twice daily) increased energy expenditure, reduced fat mass accumulation, and improved insulin sensitivity without affecting food intake or requiring physical activity. Notable effects include a 12% body weight reduction and tenfold less fat gain in obese mice over a 28-day treatment period. Additionally, SLU-PP-332 shows potential in improving cardiac function in heart failure models by enhancing mitochondrial ultrastructure and upregulating oxidative phosphorylation pathways.

SLU-PP-332 also exhibits anti-inflammatory properties by modulating cytokine production (e.g., IL-6, TNF-α) and may inhibit angiotensin-converting enzyme 2 (ACE2), suggesting potential applications in reducing SARS-CoV-2 entry points in adipose tissue. Its ability to enhance glycogen storage and muscle protein synthesis further supports its role in metabolic optimization and muscle preservation.

Supplied by Evox Biolabs, SLU-PP-332 is available in vials containing 5 mg or 10 mg of the compound, with a purity exceeding 90%, suitable exclusively for research purposes. Currently in preclinical development, SLU-PP-332 is intended for research use only and is not approved for human or clinical applications. Its solubility, stability, and biological activity make it a promising candidate for studying metabolic disorders, including obesity, type 2 diabetes, and heart failure, as well as for exploring exercise-mimetic therapies. For batch-specific data, refer to supplier Certificates of Analysis.

References:

• Billon C, et al. ACS Chem Biol. 2023;18(4):756-771.

• ACS Chemical Biology, 2023; Journal of Pharmacology and Experimental Therapeutics; American Chemical Society presentations.