SLU-PP-332

SLU-PP-332 5mg

SLU-PP-332 is a small molecule agonist targeting the estrogen-related receptors (ERRs). These receptors are recognized as critical drivers of cellular bioenergetics and metabolic adaptation. Research in animal models positions SLU-PP-332 as a potent exercise mimetic that generates several significant physiological effects:

• Energy Metabolism Boost: Directly increases overall caloric expenditure by accelerating the pathways of fatty acid oxidation (fat burning).
• Functional Capacity: Dramatically improves physical stamina and aerobic exercise performance.
• Cellular Efficiency: Promotes mitochondrial biogenesis—the production of new power-generating organelles—and enhances their operational efficiency in muscle and cardiac tissues.

SLU-PP-332 Overview

The positive impact of regular physical activity on systemic health—ranging from enhanced cardiovascular function and improved mood to robust protection against chronic metabolic diseases—is well-documented. Developing a single pharmaceutical agent that can safely and effectively reproduce these complex, widespread benefits has been a persistent goal in biomedical research. The discovery of SLU-PP-332 represents a major scientific achievement in this pursuit, as the compound effectively mimics numerous beneficial cellular adaptations of exercise.

SLU-PP-332 is a non-peptide molecule and a highly selective estrogen-related receptor (ERR) agonist, preferentially activating the alpha and gamma subclasses (ERRalpha and ERRgamma). Preclinical data indicates that SLU-PP-332 provides comprehensive metabolic and functional support: it notably increases skeletal muscle endurance, assists in weight loss by enhancing the body's use of fat as a fuel source, contributes to cardiovascular health improvement, and shows potential for neuroprotection against age-related decline. SLU-PP-332 is rapidly emerging as an indispensable tool for researchers exploring the molecular basis of physical conditioning and metabolic disease.

SLU-PP-332 Structure

The molecular architecture of SLU-PP-332 is carefully designed to ensure high bioavailability and target engagement, allowing for robust and meaningful results in in vivo research (studies conducted in living subjects).

Estrogen-related receptors (ERRs) belong to the nuclear receptor superfamily. It is a critical scientific point that ERRs are not activated by estrogen. The name is solely historical, derived from the original genetic sequence similarity of ERRalpha to the conventional estrogen receptor gene.

ERRs are master transcriptional regulators that govern gene expression pathways responsible for energy homeostasis, oxidative capacity, and mitochondrial biogenesis. The three subtypes contribute to metabolic function in distinct ways:

ERR Subtype

Primary Function/Role

Key Tissues/Systems

ERRalpha

The primary metabolic sensor, regulating fatty acid oxidation, glucose synthesis (gluconeogenesis), and adaptive stress responses, including thermogenesis.

Heart, Skeletal Muscle, Liver, Brown Adipose Tissue

ERRgamma

Essential for regulating mitochondrial quantity (content) and activity in high-energy-demand tissues. Involved in neuronal and renal metabolism.

Muscle, Heart, Brain, Kidney

ERRbeta

Plays a major role in developmental biology, controlling the transition of pluripotent stem cells and contributing to tissue repair and growth.

Embryonic Stem Cells, Developmental Tissues

The agonism of ERRalpha and ERRgamma by SLU-PP-332 activates genetic programs that dramatically raise energy expenditure and enhance the utilization of fats for fuel through fatty acid oxidation. This action is coupled with the necessary enhancement of mitochondrial health in muscle and heart tissue, leading directly to improved physical capacity and cardiac resilience.

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's potent effect is rooted in its ability to modulate cellular respiration, the fundamental process of ATP generation primarily governed by the mitochondria.

• Targeting Mitochondria: Exercise naturally stimulates mitochondrial biogenesis and improves the overall efficiency of energy transfer. SLU-PP-332 successfully mirrors these mitochondrial adaptations at the cellular level. The resultant increase in mitochondrial density and function is associated with systemic benefits, including a higher basal metabolic rate, improved glucose tolerance, reduced insulin resistance, and enhanced aerobic stamina.
• Superior In Vivo Profile: A key attribute of SLU-PP-332 is its successful design for high bioavailability. This allows the compound to achieve effective therapeutic concentrations at target receptors throughout the body, making it a viable agent for rigorous in vivo research (in living organisms). This is a substantial step beyond previous ERR agonists, many of which were limited to in vitro studies due to metabolic instability.
• ERRalpha Agonist Breakthrough: SLU-PP-332 is one of the first functionally successful ERRalpha agonists to be developed. This is a significant accomplishment, given the challenging nature of targeting this essential metabolic regulator, and it greatly expands research into the molecular control of physical conditioning and metabolic disease.

SLU-PP-332 and Endurance Enhancement

Preclinical studies demonstrated a dramatic improvement in the physical capacity of non-obese mouse models treated with SLU-PP-332. The compound enabled the animals to run for 70% longer in duration and cover 45% greater distance compared to untreated control groups.

• Aerobic Capacity: This notable boost in endurance is a direct outcome of enhanced cellular energy production, which allows muscle tissue to sustain highly efficient aerobic metabolism for extended periods, significantly delaying fatigue.
• Fat Mobilization: To support this extended effort, the compound facilitates a critical metabolic shift towards the preferential use of internal fat stores (fat oxidation), which is necessary for sustained endurance activity and promotes metabolic efficiency.
• Microvascular Development: Activation of ERRgamma also promotes angiogenesis, resulting in increased vascular density in skeletal muscle. This improved blood supply optimizes the delivery of oxygen and nutrients while efficiently removing metabolic byproducts, directly boosting endurance and supporting metabolic health.

SLU-PP-332 and Muscle Function

The body's natural response to the stress of exercise is to increase the expression of ERRs in skeletal muscle to enhance oxygen and nutrient utilization. SLU-PP-332 mimics this endogenous signal, stimulating ERR expression in muscle tissue even in a resting state. This molecular action enhances mitochondrial function, optimizes energy synthesis, and leads to measurable improvements in skeletal muscle performance and endurance capacity.

SLU-PP-332 and Heart Health

SLU-PP-332 acts as a comprehensive pan-ERR agonist, engaging all three receptor subtypes. In models of pressure overload-induced cardiac failure, the compound displayed multiple protective effects:

• Pumping Efficacy: Demonstrated an improved ejection fraction, indicating enhanced heart muscle contractility.
• Tissue Protection: Led to a significant reduction in cardiac fibrosis, preventing the debilitating accumulation of non-functional scar tissue.
• Survival: Resulted in increased survival rates in affected mouse models.

By normalizing fatty acid oxidation and assisting the heart in restoring energy homeostasis, SLU-PP-332 holds promise for research into cardiovascular support and recovery from cardiac injury.

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

Research on Parkinson’s disease (PD) suggests that mitochondrial dysfunction is a central event leading to the characteristic loss of dopaminergic neurons.

• Neuronal Vulnerability: The neurons affected in PD are highly sensitive to oxidative stress and energy disruption. Improving mitochondrial performance is therefore a major therapeutic strategy.
• ERRgamma’s Role: ERRgamma is essential for maintaining mitochondrial content and function in neurons, supporting energy production and synaptic health. Studies indicate that activation of ERRgamma may offer protection against alpha-synuclein-related toxicity and slow disease progression.
• Therapeutic Investigation: As a potent activator of ERRgamma, SLU-PP-332 is a valuable molecular tool for investigating strategies to preserve neuronal integrity and potentially modify the progression of neurodegenerative conditions.

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

The anti-aging and healthspan benefits of long-term caloric restriction (CR) are scientifically established, with research linking these benefits to the maintenance of high ERR signaling levels.

• Age-Related Decline: Studies in highly metabolic organs, such as the kidney, show that ERR levels decline with age, a decline prevented in CR animals.
• CR Mimicry: SLU-PP-332, notably 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, paralleling the healthspan benefits seen with CR without the need for dietary intervention.
• Mitochondrial Basis of Aging: Mitochondrial decline is a primary hallmark of aging, driving increased oxidative stress and cellular senescence. By directly enhancing mitochondrial health, SLU-PP-332 offers a unique research avenue for investigating interventions to mitigate age-related metabolic decay.

Other ERR Agonists in Research

SLU-PP-332 is a prominent compound among the ERR agonists under active investigation, including SLU-PP-1072 and SLU-PP-915.

• SLU-PP-1072: This structurally similar analog also targets ERRalpha and ERRgamma. Its research has focused primarily on its ability to induce apoptosis (cell death) in prostate cancer cell lines.
• SLU-PP-915: While structurally different, SLU-PP-915 shares the cardioprotective benefits seen with SLU-PP-332, including improved cardiac function and reduced fibrosis after injury, underscoring the vital role of ERR signaling in cardiac metabolism.

SLU-PP-332: Summary

SLU-PP-332 is a non-peptide, highly bioavailable estrogen-related receptor agonist that preferentially engages ERRalpha and ERRgamma. Its central mechanism is the powerful promotion of mitochondrial function and biogenesis, which results in significant improvements in cellular energy dynamics.

The compound's primary functional effect is a dramatic increase in exercise capacity and endurance. Secondary research indicates utility in cardiovascular support, anti-aging research, and neuroprotection. SLU-PP-332 is a critical research tool for advancing our understanding of metabolic adaptation and human performance physiology.

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 serves as a Professor of Medicine and Director of the Center for Cardiovascular Research at Washington University School of Medicine in St. Louis. His specialized research areas include nuclear receptor signaling, cardiac energetics, and mitochondrial metabolism.

Scientific Journal Author

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

Dr. Giguere is a recognized authority 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 in this product description 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 undergo the precise stabilization process of lyophilization (freeze-drying), ensuring the peptide's integrity and stability during shipment for approximately 3–4 months. Lyophilization is a dehydration technique where the peptide is first frozen, and water is then removed through sublimation (solid-to-gas transition) under vacuum. This yields a highly stable, white crystalline powder, the lyophilized peptide, which can be safely stored at room temperature until it requires reconstitution.

• Short-Term Storage (Days to Months): Upon receipt, the product should be kept in a cool, dark location. For short-term use, refrigeration below 4 degrees C (39 degrees F) is suitable. Lyophilized peptides typically maintain stability at room temperature for several weeks, which is acceptable for short-duration storage.
• Long-Term Storage (Months to Years): To achieve maximum stability and product longevity, the lyophilized peptide should be stored in a freezer at -20 degrees C (-4 degrees F) or colder, with -80 degrees C (-112 degrees F) being optimal for extended periods.
• Post-Reconstitution Storage: Once the peptide is reconstituted with bacteriostatic water, the resultant solution must be stored in a refrigerator (4 degrees C). Under these refrigerated conditions, the solution remains stable for up to 30 days.

Best Practices For Storing Peptides

Following correct storage procedures is essential for maintaining the accuracy and reliability of research outcomes. Proper handling minimizes risks of degradation, oxidation, and contamination.

• Minimize Freeze-Thaw Cycles: Repeated fluctuations in temperature severely compromise peptide integrity. Researchers should avoid using frost-free freezers as their temperature cycling is detrimental. To prevent repeated exposure, the peptide should be partitioned into small, single-use aliquots immediately upon receipt.
• Prevent Oxidation and Moisture Contamination: Air and moisture are the primary causes of peptide degradation.
• Thawing Protocol: When removing a vial from the freezer, it is mandatory to allow it to reach room temperature completely before opening. This prevents damaging condensation (moisture) from forming on the cold powder.
• Air Exclusion: Keep the container sealed as much as possible. After removing the necessary amount, the container must be promptly and securely resealed. For peptides prone 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 recommended.
• Storing Peptides In Solution: Peptides stored in solution have significantly reduced stability and a shorter shelf life compared to their lyophilized form.
• If solution storage is unavoidable, use sterile, slightly acidic buffers (pH 5 to 6).
• Aliquot the solution to prevent repeated freeze-thaw cycles.
• Solutions are generally 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 should be clean, chemically inert, durable, and sized appropriately to minimize air space.

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

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.
• Prioritize lyophilized storage; avoid extended storage in solution.
• Aliquot the product to match experimental needs.