SLU-PP-332 250mcg x 100ct

Compound Name: SLU-PP-332

Synonyms: 4-Hydroxy-N-[(Z)-naphthalen-2-ylmethylideneamino]benzamide

CAS Number: 303760-60-3

Molecular Formula: C₁₈H₁₄N₂O₂

Molecular Weight: ~290.3 g/mol

Structure: Small molecule hydrazone derivative with naphthalene substitution optimized for ERRα binding

Peptide Sequence: N/A; Not a peptide

Chemical Structure:

Source: PubChem

Mechanism of Action: SLU‑PP‑332 directly binds the ligand‑binding domains of ERRα, ERRβ, and ERRγ, stabilizing the active conformation and enhancing transcription of ERR‑regulated metabolic genes. This results in elevated expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes, fatty acid oxidation (FAO) enzymes, and contractile proteins in muscle and heart. ERRα activation drives an acute aerobic exercise gene program, including rapid up‑regulation of Ddit4 and Slc25a25, supporting metabolic remodeling and endurance enhancement^1-4.

Biological Activity: SLU‑PP‑332 increases oxidative type IIa muscle fibers, boosts mitochondrial density, raises resting energy expenditure, shifts substrate preference toward lipids, and reduces adiposity in diet‑induced obesity and ob/ob mouse models^2,3. In cardiac disease models, it restores contractile function, enhances FAO, attenuates fibrosis, and improves survival without worsening hypertrophy⁴.

Storage: Store at –20°C. Protect from light.

Drug Categories: Exercise mimetic; metabolic modulator; mitochondrial enhancer; nuclear receptor agonist

Additional Notes:

For research use only. Emerging therapeutic potential for obesity, type 2 diabetes, metabolic syndrome, heart failure, and sarcopenia.

Summary Table:

Disclaimer: For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

Detailed Product Description

SLU‑PP‑332 represents a breakthrough in the development of pharmacological exercise mimetics. Created via structure‑guided optimization of the ERRβ/γ agonist GSK4716, it incorporates a naphthalene group that enables high‑affinity π–π interactions with ERRα, resulting in a ~50‑fold increase in ERRα potency compared with the parent scaffold¹. This design confers robust activation of all three ERR isoforms, with the greatest selectivity for ERRα, allowing SLU‑PP‑332 to both mimic and amplify aerobic training–induced adaptations.

In skeletal muscle, SLU‑PP‑332 stimulates an ERRα‑dependent acute aerobic exercise program, rapidly inducing key mitochondrial control genes and shifting fuel utilization toward fatty acids¹². In vivo, treatment enhances endurance performance by ~70% and promotes oxidative fiber remodeling without increasing activity levels¹. In obesity models, SLU‑PP‑332 reduces fat gain to near‑zero over four weeks, improves glucose tolerance, and elevates energy expenditure without altering food intake^2,3. In heart failure due to pressure overload, it restores ejection fraction, improves mitochondrial ultrastructure, boosts FAO enzymes, and reduces fibrosis⁴.

Research Highlights

• Exercise Mimetic and Endurance Enhancement: Demonstrated to activate an ERRα‑dependent acute aerobic exercise gene program, increase oxidative type IIa skeletal muscle fibers, upregulate oxidative phosphorylation proteins, and improve mitochondrial content, leading to ~70% longer running time and ~45% greater running distance in preclinical treadmill tests¹.
• Mitochondrial Biogenesis and Metabolic Remodeling: Stimulates mitochondrial respiration, increases cytochrome c levels, enhances oxidative phosphorylation complex abundance, and shifts substrate preference toward fatty acid oxidation via upregulation of Pdk4; these changes collectively improve metabolic efficiency in muscle and heart tissue^1,3.
• Cardioprotective Effects in Heart Failure: In a pressure‑overload heart failure mouse model, restores fatty acid metabolism, improves mitochondrial function, elevates ejection fraction, reduces fibrosis, and normalizes tricarboxylic acid (TCA) and oxidative phosphorylation intermediates without inducing adverse cardiac hypertrophy³.
• Anti‑Obesity and Metabolic Benefits: In diet‑induced obese mice, reduces body weight by ~12% and limits fat mass gain despite unchanged food intake, through mechanisms involving increased whole‑body energy expenditure, amplified fatty acid oxidation, and ERR‑mediated metabolic pathway activation².

Mechanism of Action

ERRα Agonism

• Primary driver of acute aerobic exercise genetic program¹.
• Induces Ddit4 and Slc25a25 expression, improving mitochondrial efficiency and endurance^1,2.
• Promotes fatty acid oxidation via upregulation of Pdk4, reducing carbohydrate reliance¹.
• Activates oxidative metabolism pathways, increasing energy efficiency in muscle and heart tissue².

ERRβ Agonism

• Contributes to cardiac contractile function and oxygen utilization³.

• Less characterized but may support mitochondrial baseline activity and metabolic homeostasis³.

ERRγ Agonism

• Supports increased angiogenesis, mitochondrial density, and endurance adaptation³.

• Major mediator of cardiac oxidative metabolism improvements observed in heart failure³.

Pharmacokinetic Profile:

• Route of Administration: Oral
• Dosing Frequency: Twice daily
• Half‑Life: Short in plasma; sustained tissue exposure noted in muscle

Formulation & Handling

• Solid powder
• Store at –20 °C, protected from light.

Selected Clinical Trial Activity

SLU-PP-332 is a research-grade compound that has been studied in laboratory settings but has not undergone full clinical development. It is not approved for therapeutic use in humans, and no large-scale clinical trials have been conducted to evaluate its safety or efficacy as a medication. SLU-PP-332 is supplied strictly for laboratory research and investigational purposes only.

References

¹Billon, C., Sitaula, S., Banerjee, S., Welch, R., Elgendy, B., Hegazy, L., Oh, T. G., Kazantzis, M., Chatterjee, A., Chrivia, J. et al. Synthetic ERRα/β/γ agonist induces an ERRα‑dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem. Biol. 18, 756–771 (2023).

²Nasri, H. New hopes on “SLU‑PP‑332” as an effective agent for weight loss with indirect kidney protection efficacy; a nephrology point of view. J. Ren. Endocrinol. 10, e25143 (2024).

³Xu, W., Billon, C., Li, H., Welch, R., Banerjee, S., Chatterjee, A., Kazantzis, M., Elgendy, B., Hegazy, L., Oh, T. G. et al. Novel pan‑ERR agonists ameliorate heart failure through enhancing cardiac fatty acid metabolism and mitochondrial function. Circulation (2024).

⁴Billon, C., Schoepke, E., Avdagic, A., Chatterjee, A., Butler, A. A., Elgendy, B., Welch, R., Kazantzis, M., Banerjee, S., Hegazy, L. et al. A synthetic ERR agonist alleviates metabolic syndrome. J. Pharmacol. Exp. Ther. (2023).