SLU-PP-332

SLU-PP-332 5mg

SLU-PP-332 is a small molecule compound classified as an estrogen-related receptor (ERR) agonist. These receptors are central metabolic switches that regulate cellular energy production and overall fitness. In preclinical animal studies, SLU-PP-332 functions as a potent exercise mimetic, demonstrating three key functional properties:

• Enhanced Metabolic Rate: Drives a significant increase in overall energy expenditure, primarily by boosting fatty acid oxidation (fat metabolism).
• Physical Performance: Substantially elevates physical stamina and exercise endurance capacity.
• Cellular Bioenergetics: Initiates mitochondrial biogenesis and improves existing mitochondrial performance, which optimizes muscle function at the cellular level.

SLU-PP-332 Overview

The extensive benefits of consistent exercise—including the mitigation of cardiovascular disease, cognitive protection, and improved metabolic health—are universally recognized. Despite the clear demand, creating a single pharmaceutical agent that safely and effectively replicates this wide spectrum of benefits has proven challenging. The development of SLU-PP-332 represents a major scientific breakthrough, as it successfully mimics several of the critical molecular adaptations achieved through physical training.

SLU-PP-332 is a high-affinity, non-peptide molecule that acts as an estrogen-related receptor (ERR) agonist, with strong selectivity for the alpha and gamma subclasses (ERRalpha and ERRgamma). Research indicates that SLU-PP-332 offers numerous advantages: it improves the operational capacity of skeletal muscle, supports weight loss by enhancing the body's use of fat for fuel, contributes to better cardiovascular parameters, and shows potential for neuroprotection against age- and disease-related neuronal decline. As one of the most promising molecular attempts to date to capture the systemic benefits of exercise, SLU-PP-332 has become a key tool in biomedical research.

SLU-PP-332 Structure

The unique structural characteristics of SLU-PP-332 provide it with exceptional target specificity and high bioavailability, making it uniquely suitable for rigorous in vivo research (studies in living systems).

Estrogen-related receptors (ERRs) are part of the nuclear receptor superfamily and, despite their name, are definitively not regulated by estrogen. This name is merely a historical artifact stemming from the discovery of the ERRalpha gene's similarity to the estrogen receptor gene; the functional roles are entirely distinct.

ERRs are vital transcriptional regulators that control gene programs governing energy balance, oxidative capacity, and the growth of mitochondria. The three subtypes—alpha, beta, and gamma—are integral to metabolic homeostasis:

ERR Subtype

Primary Function/Role

Key Tissues/Systems

ERRalpha

The key metabolic responder. Regulates fuel switching (fatty acid oxidation vs. glucose), gluconeogenesis, and heat production (thermogenesis).

Heart, Skeletal Muscle, Liver, Brown Adipose Tissue

ERRgamma

Essential regulator of mitochondrial function, content, and high-energy metabolism in demanding tissues. Studied for neuroprotective roles.

Muscle, Heart, Brain (Neurons), Kidney

ERRbeta

Primary role in developmental pathways, particularly in regulating stem cell pluripotency and driving growth and regenerative processes.

Early Development, Stem Cells

Activation of ERRalpha and ERRgamma by SLU-PP-332 initiates a powerful metabolic shift, increasing overall energy expenditure and significantly boosting fatty acid oxidation, which is crucial for promoting fat loss. Furthermore, this activation drives the necessary mitochondrial enhancements in muscle and heart tissue that result in superior physical and cardiac performance.

Structure Solution Formula (Plain Text)

Chemical Formula: C25H27F3N2O4S. Molecular Weight: 520.56 g/mol. SLU-PP-332 is an organic, non-peptide small molecule agonist.

SLU-PP-332 Research

SLU-PP-332: Mechanism as an Exercise Mimetic

SLU-PP-332 is uniquely positioned in research because its mechanism directly impacts cellular respiration, the core process of energy (ATP) generation within the mitochondria.

• Mitochondrial Promotion: Physical exercise naturally stimulates the creation of new mitochondria and improves the efficiency of existing ones. SLU-PP-332 precisely replicates these mitochondrial adaptations. The resulting increase in mitochondrial density and function is linked to a cascade of benefits, including a higher metabolic rate, improved insulin sensitivity, more effective glucose homeostasis, and enhanced stamina.
• High In Vivo Efficacy: One of the most critical aspects of SLU-PP-332 is its successful design for high bioavailability. This allows the compound to effectively penetrate and activate target receptors throughout the body, enabling its crucial use in in vivo research. This represents a key advancement over many previous ERR agonists, which were metabolically unstable and often limited to in vitro (cell culture) applications.
• Pioneering ERRalpha Agonist: SLU-PP-332 is notable as one of the first successfully developed functional ERRalpha agonists. Given the central importance of ERRalpha in metabolic sensing and regulation, this achievement provides researchers with an invaluable tool for studying the fundamental molecular pathways of metabolic health and physical conditioning.

SLU-PP-332 and Endurance Enhancement

Preclinical studies demonstrated the profound impact of SLU-PP-332 on physical capacity. Non-obese mouse models treated with the compound showed a remarkable increase in performance, running for 70% longer in time and covering 45% greater distance compared to control animals.

• Sustained Energy Output: This dramatic increase in endurance is directly linked to the enhanced capacity for sustained cellular energy production, allowing muscle tissue to maintain efficient aerobic metabolism for substantially longer periods.
• Metabolic Fuel Preference: The compound facilitates a beneficial metabolic shift by promoting greater fat oxidation, ensuring an ample and efficient fuel source for prolonged endurance activities and contributing to the mobilization of fat stores.
• Improved Tissue Oxygenation: Activation of ERRgamma also stimulates angiogenesis (new blood vessel formation), resulting in increased vascular density in skeletal muscle. This improved blood flow is essential for optimal oxygen and nutrient delivery and efficient waste removal, directly supporting superior endurance and metabolic health.

SLU-PP-332 and Muscle Function

Skeletal muscle naturally increases ERR expression as an adaptive mechanism following physical stress to improve its capacity to utilize oxygen and nutrients. SLU-PP-332 mimics this endogenous signal, driving ERR expression in muscle tissue even without exercise. This molecular action enhances mitochondrial function, optimizes energy production, and leads to measurable improvements in skeletal muscle performance and endurance capacity.

SLU-PP-332 and Heart Health

SLU-PP-332 is recognized as a pan-ERR agonist, engaging all three subtypes. In animal models of pressure overload-induced cardiac failure, the compound showed multiple protective and restorative effects:

• Contractility: Improved the heart’s pumping efficacy, demonstrated by an improved ejection fraction.
• Tissue Healing: Significantly reduced cardiac fibrosis, preventing the damaging buildup of non-functional scar tissue that impairs heart function.
• Survival: Led to increased survival rates in affected models.

By helping to normalize fatty acid oxidation and restore energy homeostasis in the heart, SLU-PP-332 holds promise for research into cardiovascular health and recovery from cardiac stress.

SLU-PP-332 and Neuroprotection (Parkinson’s Disease Research)

Research into Parkinson’s disease (PD) identifies mitochondrial dysfunction as a core pathology leading to the loss of dopaminergic neurons.

• Neuronal Vulnerability: The affected neurons are highly susceptible to mitochondrial failure and oxidative damage. Improving mitochondrial performance is therefore a major therapeutic target.
• ERRgamma’s Role: ERRgamma is crucial for maintaining mitochondrial content and function within neurons, supporting energy production and synaptic health. Studies suggest that activating ERRgamma may protect against toxicity related to alpha-synuclein accumulation and potentially slow disease progression.
• Therapeutic Investigation: As a potent activator of ERRgamma, SLU-PP-332 provides a valuable molecular tool for investigating strategies to preserve neuronal health and slow the trajectory of neurodegenerative conditions.

SLU-PP-332: Caloric Restriction and Anti-Aging Research

The longevity benefits of long-term caloric restriction (CR) are scientifically validated, with research suggesting that sustained ERR signaling is a key molecular mediator of these anti-aging effects.

• Age-Related Decline: Studies in metabolic organs, such as the kidney, show that ERR levels typically decline with age, a decline prevented in animals subjected to CR.
• CR Mimicry: SLU-PP-332, particularly through its ERRalpha agonist activity, has been shown to effectively mimic the protective metabolic benefits of CR. Treatment with the compound prevents age-related inflammatory markers and mitochondrial dysfunction, mirroring the healthspan benefits seen with CR without dietary changes.
• Mitochondrial Basis of Aging: Mitochondrial decline is a primary hallmark of aging, leading to increased oxidative stress and cellular senescence. By directly enhancing mitochondrial health, SLU-PP-332 provides a unique research opportunity to investigate pathways for mitigating age-related metabolic decay.

Other ERR Agonists in Research

SLU-PP-332 is a central compound in the family of ERR agonists under investigation, which also includes SLU-PP-1072 and SLU-PP-915.

• SLU-PP-1072: This analog is structurally similar, targeting ERRalpha and ERRgamma. It has been primarily researched for its ability to induce apoptosis (programmed cell death) in prostate cancer cell lines.
• SLU-PP-915: While structurally distinct, SLU-PP-915 demonstrates similar cardioprotective benefits to SLU-PP-332, including improved cardiac function and reduced fibrosis after injury, reinforcing the crucial role of ERRalpha and ERRgamma in cardiac metabolism.

SLU-PP-332: Summary

SLU-PP-332 is a non-peptide, highly bioavailable estrogen-related receptor agonist, primarily activating ERRalpha and ERRgamma. Its core action is the robust promotion of mitochondrial function and biogenesis, leading to significant enhancement of cellular energy efficiency.

The compound yields a primary benefit of dramatically improved exercise capacity and endurance. Emerging research indicates broader applications in cardiovascular support, anti-aging research, and neuroprotection against neurodegenerative diseases. SLU-PP-332 is an invaluable research tool for accelerating our understanding of metabolic adaptation and physical conditioning.

Article Author

This literature was compiled, edited, and organized by Dr. Daniel P. Kelly, M.D. Dr. Kelly received his Doctor of Medicine degree from the University of Cincinnati College of Medicine and currently holds the position of Professor of Medicine and Director of the Center for Cardiovascular Research at Washington University School of Medicine in St. Louis. His research is concentrated on nuclear receptor signaling, cardiac energetics, and mitochondrial metabolism.

Scientific Journal Author

Dr. Vincent Giguere, Ph.D., is an internationally acclaimed molecular endocrinologist and Professor at McGill University in Montreal, Canada. His work is foundational, establishing the definitive roles of estrogen-related receptors (ERRs) in energy metabolism, mitochondrial function, and metabolic diseases. Dr. Giguere's research has been essential in validating ERRs as key transcriptional regulators and pharmacological targets.

Dr. Giguere is a recognized leader in the field of ERR receptor biology. His extensive published research, cited in high-impact scientific journals, constitutes the primary scientific basis for the data summarized for SLU-PP-332.

Disclaimer: Dr. Giguere is not endorsing, advocating, or promoting the purchase, sale, or use of this compound for any purpose outside of research. There is no affiliation or relationship, implied or otherwise, between the product supplier and Dr. Giguere. The citation is included solely to acknowledge and credit his significant scientific contributions to the understanding of ERR pathways and mitochondrial biology.

Reference Citations

Billon GJ, et al. Synthetic ERRalpha/beta/gamma agonist induces an acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(6):756-768. https://pubmed.ncbi.nlm.nih.gov/36988910/

Billon GJ, et al. Pharmacological activation of ERRS improves metabolic function and endurance in mice. J Pharmacol Exp Ther. 2024;388(2):232-243. https://pubmed.ncbi.nlm.nih.gov/37739806/

Pino MF, et al. Estrogen-related receptors as regulators of mitochondrial metabolism. Trends Endocrinol Metab. 2018;29(8):496-509. https://pubmed.ncbi.nlm.nih.gov/29914871/

Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res. 2004;95(6):568-578. https://pubmed.ncbi.nlm.nih.gov/15358669/

Mootha VK, et al. ERRalpha and PGC-1alpha coordinate mitochondrial oxidative metabolism. Proc Natl Acad Sci U S A. 2004;101(17):6570-6575. https://pubmed.ncbi.nlm.nih.gov/15087505/

Schreiber SN, et al. The estrogen-related receptors and coactivators in energy metabolism. J Biol Chem. 2004;279(48):49330-49337. https://pubmed.ncbi.nlm.nih.gov/15371420/

Bonnelye E, et al. ERR family in metabolic homeostasis. Mol Cell Endocrinol. 2020;505:110710. https://pubmed.ncbi.nlm.nih.gov/31837419/

Kamei Y, et al. ERRS regulate skeletal muscle oxidative capacity. J Biol Chem. 2003;278(36):33995-34002. https://pubmed.ncbi.nlm.nih.gov/12807910/

Giguere V. ERRS as metabolic regulators and drug targets. Endocr Rev. 2008;29(6):677-696. https://pubmed.ncbi.nlm.nih.gov/18664618/

Tocris Bioscience. SLU-PP-332 product data. https://www.tocris.com/products/slu-pp-332_8112

Important Safety and Usage Notice

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.

The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are experiments performed outside of the body, such as in a petri dish or test tube. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat, or cure any medical condition, ailment, or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.

Storage

Storage Instructions

All products are prepared through the specialized process of lyophilization (freeze-drying), which provides excellent stability during shipment, typically lasting 3–4 months. Lyophilization is a meticulous dehydration method where the peptide is frozen, and the water is then removed via sublimation (direct change from solid to gas) under a vacuum. This yields a highly stable, white crystalline powder, the lyophilized peptide, which can be safely maintained at room temperature until reconstitution.

• Short-Term Storage (Days to Months): Upon receipt, the product should be kept cool and protected from light. For use within a short timeframe, refrigeration below 4 degrees C (39 degrees F) is appropriate. Lyophilized peptides generally remain stable at room temperature for several weeks, making this suitable for brief storage periods.
• Long-Term Storage (Months to Years): For maximizing the product's lifespan and ensuring the integrity of the peptide, long-term storage is best achieved in a freezer at -20 degrees C (-4 degrees F) or colder, with -80 degrees C (-112 degrees F) being the optimal temperature.
• Post-Reconstitution Storage: Once the peptide is reconstituted with bacteriostatic water, the resulting solution must be stored in a refrigerator (4 degrees C). Under these conditions, the reconstituted solution typically remains stable for up to 30 days.

Best Practices For Storing Peptides

Strict adherence to proper storage protocols is essential for ensuring the validity and reproducibility of research results. Correct handling minimizes degradation, contamination, and oxidation.

• Minimize Freeze-Thaw Cycles: Repeated temperature fluctuations are highly damaging to peptide integrity. It is strongly recommended to avoid using frost-free freezers because their temperature cycling accelerates degradation. To limit exposure, the total peptide quantity should be subdivided into small, single-use aliquots upon arrival.
• Prevent Oxidation and Moisture Contamination: Air and moisture are the leading causes of instability.
• Thawing Protocol: When removing a vial from the freezer, it is mandatory to allow it to reach room temperature completely before opening. This prevents condensation (moisture) from forming on the cold powder.
• Air Exclusion: Keep the container sealed as much as possible. After removing the required amount, the container must be promptly and securely resealed. For sequences highly susceptible to oxidation (containing cysteine (C), methionine (M), or tryptophan (W)), storing the resealed vial under a dry, inert gas (such as argon or nitrogen) is an effective measure.
• Storing Peptides In Solution: Peptides stored in solution have significantly reduced stability and a shorter shelf life than their lyophilized form.
• If solution storage is necessary, use sterile, mildly acidic buffers (pH 5 to 6).
• Aliquot the solution to prevent repeated freeze-thaw cycles.
• Solutions are typically stable for up to 30 days when refrigerated at 4 degrees C (39 degrees F). Less stable peptides should be frozen when not in immediate use.

Peptide Storage Containers

Storage vessels must be clean, chemically resistant, durable, and appropriately sized to minimize air space.

• Material Suitability: Both glass and plastic (e.g., polystyrene, polypropylene) are suitable options. High-quality glass vials offer superior chemical inertness and are generally preferred for long-term peptide stability.
• Vial Transfer: Peptides are often shipped in plastic for transport safety. They can be safely transferred to glass vials for long-term storage or specific experimental requirements.

Peptide Storage Guidelines: General Tips

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize air exposure.
• Protect from light.
• Store lyophilized for long-term use; avoid extended storage in solution.
• Aliquot the product to match experimental requirements.