SLU-PP-332(60 Capsules, 250mcg/capsule)

SLU-PP-332 is a synthetic agonist of estrogen receptor-related orphan receptors (ERRs) that acts as an exercise mimetic, meaning it can trigger some of the same metabolic and physiological effects as physical exercise.

Research in animal models shows that SLU-PP-332 enhances energy metabolism, improves endurance, and reduces fat mass, suggesting potential in metabolic disease research.

Mechanisms of Action

SLU-PP-332 activates all three ERR subtypes, with the highest potency for ERRα. This activation leads to increased mitochondrial function, enhanced cellular respiration, and upregulation of genes involved in fatty acid metabolism and oxidative phosphorylation.^[1]

In skeletal muscle, it induces an acute aerobic exercise genetic program, increases oxidative type IIa muscle fibers, and boosts energy expenditure and fatty acid oxidation.^[1]

In the heart, ERR agonism primarily mediated by ERRγ enhances mitochondrial capacity and normalizes metabolic profiles.^[2]

In the kidney, SLU-PP-332 reverses age-related mitochondrial dysfunction and inflammation, acting through pathways such as cGAS-STING and STAT3.^[3]

Exercise Mimetic and Metabolic Effects

SLU-PP-332 mimics exercise-induced metabolic effects, improving endurance, reducing fat mass, and increasing energy expenditure in mouse models.^[4][5] 

The peptide effectively reduces obesity and improves insulin sensitivity in models of metabolic syndrome, suggesting potential for treating obesity, type 2 diabetes, and related disorders.^[4][5]

Cardioprotective Effects

SLU-PP-332 significantly improves ejection fraction, reduces fibrosis, and increases survival in mouse models of pressure overload-induced heart failure. These effects occur without affecting cardiac hypertrophy.^[2]

ERR agonists, including SLU-PP-332, induce autophagy in cardiomyocytes and downregulate cell cycle and developmental pathways, partly through E2F1 modulation.^[2]

By maintaining oxidative metabolism and supporting mitochondrial function, SLU-PP-332 confers robust cardiac protection in heart failure models.^[2]

The cardioprotective effects are specifically mediated by ERRγ, confirming the target specificity of SLU-PP-332 and related agonists.^[2]

Renal Protective Effects

SLU-PP-332 treatment in aged mice reversed key markers of kidney aging, including increased albuminuria (protein in urine), loss of podocytes (specialized kidney cells), mitochondrial dysfunction, and elevated inflammatory cytokines.^[3]

The molecule acts through important cellular pathways, specifically the cGAS–STING and STAT3 signaling pathways, to reduce inflammation and improve mitochondrial health.^[3]

These effects are similar to those seen with lifelong caloric restriction, a known intervention for slowing kidney aging.^[3]

In addition to direct renal effects, SLU-PP-332 reduces fat mass accumulation and improves exercise endurance, which may indirectly benefit kidney health by addressing metabolic risk factors such as obesity and insulin resistance.^[6]

Muscle Function

Animal studies show SLU-PP-332 increases the proportion of type IIa oxidative skeletal muscle fibers, which are associated with improved endurance and aerobic capacity.^[1]

Treated mice show enhanced exercise endurance, indicating improved muscle function and performance.^[1]

References

1. Billon, C., Sitaula, S., Banerjee, S., Welch, R., Elgendy, B., Hegazy, L., Oh, T., Kazantzis, M., Chatterjee, A., Chrivia, J., Hayes, M., Xu, W., Hamilton, A., Huss, J., Zhang, L., Walker, J., Downes, M., Evans, R., & Burris, T. (2023). Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity.. ACS chemical biology. https://doi.org/10.1021/acschembio.2c00720.
2. Xu, W., Billon, C., Li, H., Wilderman, A., Qi, L., Graves, A., Rideb, J., Zhao, Y., Hayes, M., Yu, K., Losby, M., Hampton, C., Adeyemi, C., Hong, S., Nasiotis, E., Fu, C., Oh, T., Fan, W., Downes, M., Welch, R., Evans, R., Milosavljevic, A., Walker, J., Jensen, B., Pei, L., Burris, T., & Zhang, L. (2023). Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation, 149, 227 – 250. https://doi.org/10.1161/CIRCULATIONAHA.123.066542.
3. Wang, X., Myakala, K., Libby, A., Krawczyk, E., Panov, J., Jones, B., Bhasin, K., Shults, N., Qi, Y., Krausz, K., Zerfas, P., Takahashi, S., Daneshpajouhnejad, P., Titievsky, A., Taranenko, E., Billon, C., Chatterjee, A., Walker, J., Albanese, C., Kopp, J., Rosenberg, A., Gonzalez, F., Guha, U., Brodsky, L., Burris, T., & Levi, M. (2023). Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney.. The American journal of pathology. https://doi.org/10.1016/j.ajpath.2023.07.008.
4. Mahale, B., Girase, A., & Mahale, M. (2024). Unlocking the potential: SLU-PP-332 and the future of exercise Enhancement and Metabolic health. Research Journal of Science and Technology. https://doi.org/10.52711/2349-2988.2024.00047.
5. Billon, C., Schoepke, E., Avdagic, A., Chatterjee, A., Butler, A., Elgendy, B., Walker, J., & Burris, T. (2023). A Synthetic ERR Agonist Alleviates Metabolic Syndrome. The Journal of Pharmacology and Experimental Therapeutics, 388, 232 – 240. https://doi.org/10.1124/jpet.123.001733.
6. Nasri, H. (2024). New hopes on “SLU-PP-332” as an effective agent for weight loss with indirect kidney protection efficacy; a nephrology point of view. Journal of Renal Endocrinology. https://doi.org/10.34172/jre.2024.25143.