CAS 303760-60-3 Slupp332 Slu pp 332 Slu-pp-332 Peptide Slu-pp-332

1.  Description

    Chemical Properties: SLU-PP-332 is a small-molecule compound belonging to the naphthylmethylenebenzohydrazide class. Its IUPAC name is “4-hydroxy-N'-(naphthyl-2-ylmethylene)benzohydrazide,” with the molecular formula C₁₈H₁₄N₂O₂ and molecular weight 290.32. benzoylhydrazide," with the molecular formula C₁₈H₁₄N₂O₂ and molecular weight 290.32. Its core mechanism of action is as a pan-ERR agonist, exhibiting highest affinity for ERRα (EC₅₀=98 nM), followed by ERRβ (EC₅₀=230 nM) and ERRγ (EC₅₀=430 nM). It regulates mitochondrial function and energy metabolism by activating the ERR signaling pathway. It lacks traditional estrogen receptor (ER)-related activity, possesses stable chemical properties, and is resistant to hydrolysis.

     Physical Properties: At room temperature, SLU-PP-332 appears as a white to off-white solid powder. Solubility exhibits significant solvent dependency: highly soluble in dimethyl sulfoxide (DMSO, maximum solubility 75 mg/mL), slightly soluble in ethanol (2 mg/mL), and insoluble in water. Research-grade products typically exhibit ≥98% purity, with select high-purity specifications reaching 99.5% (HPLC-determined). Storage conditions are stringent: powders require sealed, light-protected storage at -20°C (3-year shelf life); solvent solutions must be stored at -80°C (1-year shelf life). Avoid exposure to high temperatures, intense light, and strong oxidizing agents.

     Source and Preparation: SLU-PP-332 has no natural occurrence and is prepared via organic synthesis. Starting from 4-hydroxybenzoic acid, naphthalene-2-carboxaldehyde, and hydrazine derivatives, the core skeleton is constructed through acylation and condensation reactions. High-purity products are ultimately obtained via high-performance liquid chromatography (HPLC) purification. The synthesis process requires precise control of reaction temperature (25–30°C) and feed ratios to ensure molecular structural integrity and receptor binding activity. It is currently produced at scale by research reagent manufacturers such as Cayman Chemical and Selleck.

2.  Application

     Biomedical Research Field: SLU-PP-332 serves as a core tool reagent for studying the ERR signaling pathway and metabolic mechanisms, compatible with both cellular and animal model experiments. At the cellular level, it is used in HEK293 cells (for ERR expression validation) and C2C12 skeletal muscle progenitor cells (for mitochondrial respiratory function detection) to investigate ERR's regulatory role in fatty acid oxidation and mitochondrial biogenesis. At the animal level, it is applied in high-fat diet-induced obese mouse models and age-related kidney disease mouse models to investigate the pathological mechanisms of metabolic syndrome, organ aging, and muscle function decline, providing experimental evidence for intervention strategies in related diseases.

     Preclinical Drug Development Field: SLU-PP-332 serves as a candidate molecule for early-stage research and development of drugs targeting metabolic diseases and muscle function. For non-alcoholic fatty liver disease (NAFLD), exploring its potential to reduce hepatic fat content; for obesity and type 2 diabetes, validating its effects on improving insulin sensitivity and regulating blood glucose and lipid levels; for age- or disease-related muscle loss, investigating its role in maintaining muscle mass and enhancing muscular endurance. Currently in the animal-level activity validation phase, but human clinical trials have not yet commenced.

     Sports Nutrition and Metabolic Research: SLU-PP-332 serves as an “exercise-mimicking molecule” tool for studying metabolic support mechanisms in populations unable to exercise (e.g., the elderly, disabled individuals). Animal studies have validated its ability to “mimic aerobic training effects without exercise,” such as preserving muscle mitochondrial function and reducing muscle loss during fat loss periods. This offers new research avenues for maintaining metabolic health and muscle function in special populations, though related applications remain in the theoretical exploration phase.

3. Main Efficacy

     Metabolic Optimization and Fat Reduction Effects: The core mechanism of SLU-PP-332 is to activate ERR to regulate fatty acid oxidation (FAO) and mitochondrial respiration-related genes (such as cytochrome c and carnitine palmitoyltransferase), accelerating fat breakdown for energy production. In a high-fat diet-induced obese mouse model, daily administration at a dose of 50 mg/kg twice daily resulted in a 12% reduction in body weight and a significant decrease in fat mass after 28 days. Concurrently, serum total cholesterol and triglyceride levels decreased, glucose tolerance improved (reduced blood glucose peaks), and appetite and spontaneous activity levels remained unaffected—distinguishing it from centrally stimulating fat-reducing compounds like caffeine.

    Muscle Endurance and Functional Enhancement Effects: By activating ERRα to promote skeletal muscle mitochondrial biogenesis and oxidative fiber conversion—in normal mouse models, a 50 mg/kg dose administered twice daily increased running time by 70%, running distance by 45%, and significantly enhanced grip strength; Simultaneously increases the number of oxidative muscle fibers in the quadriceps, mitochondrial DNA (mtDNA) levels, and myosin IIa expression, enhancing muscle aerobic metabolism. This mimics the muscle remodeling effects of “aerobic training” without causing muscle damage side effects.

     Organ Protection and Anti-Aging Effects: For age-related damage, SLU-PP-332 administered at 25 mg/kg daily for 8 weeks suppressed proteinuria elevation and abnormal kidney weight in aged mouse models, increased podocyte marker (podocin) expression in kidneys, and mitigated renal injury. For the liver, it reduces hepatic fat content in high-fat diet mice and improves non-alcoholic fatty liver disease (NAFLD) pathology. Its mechanism involves ERR-mediated antioxidant effects, mitochondrial function maintenance, and inflammation suppression, offering a novel target for organ aging and metabolic organ damage research.

     Safety Advantages: No severe side effects were observed in preclinical animal studies of SLU-PP-332. Its efficacy does not depend on central nervous system stimulation, avoiding issues like palpitations and anxiety associated with traditional fat-reducing ingredients (e.g., caffeine, yohimbine). However, human clinical trial data are currently lacking, and potential long-term safety requires further validation.