SLU-PP-332 (1000mcg x 30 Capsules = 30,000mcg)

SLU-PP-332: Overview

Everyone knows that repetitive physical exercise leads to improved health and wellness. Research has repeatedly revealed that exercise can thwart heart disease, fight obesity, improve mood, boost cognitive function, and even help to prevent/treat a number of diseases. For the most part, attempts to replicate the benefits of exercise using pharmaceuticals has fallen short. Even weight loss drugs were a bust until the recent advent of peptides like semaglutide and liraglutide. A new breakthrough is underway, however, and researchers have developed a compound that can replicate some of the benefits of exercise. SLU-PP-332 is an estrogen-related receptor (ERR) agonist that binds primarily to ERR subclasses alpha and gamma. It has been shown to improve skeletal muscle endurance, boost weight loss, improve cardiovascular health, and protect the central nervous system against the ravages of aging and disease. SLU-PP-332 is the closest science has yet come to replicating the effects of exercise and has, predictably, generated a great deal of interest in research circles.

What Is SLU-PP-332?

SLU-PP-332 is one of a family of compounds known as estrogen-related receptor agonists (ERRs). Research in animal models has revealed this compound to have a number of effects including:

• Elevating energy expenditure (primarily through increased fat burning),
• Increasing exercise tolerance and physical endurance, and
• Increasing mitochondrial density and function to improve muscle function.

Research indicates that SLU-PP-332 activates the estrogen receptor-related orphan receptors, which are called ERRs for short. ERRs are found with in nucleus of cells and their endogenous (natural) ligand has yet to be unambiguously identified, which is why they are referred to as “orphans.” These receptors come in three types as follows:

It is important to note that ERRs, despite their name, are not regulated by estrogen. The name arises from the fact that the gene for ERRα was first isolated due to homology to the gene for the estrogen receptor. That is where their similarities end, however, as evidence to date indicates that estrogen plays no role in the regulation of ERRs.

These receptors are known to regulate gene expression patterns with resulting impacts on energy homeostasis, oxidative metabolism, and mitochondrial biogenesis. Stimulation of these receptors can increase energy expenditure and fatty acid oxidation, leading to an increased rate fat loss. They also enhance mitochondrial function, particularly in heart and skeletal muscle cells to improve cardiovascular health as well as exercise tolerance

One way in which scientists determined that ERRs are important to exercise tolerance is by creating mouse models, called knockouts, that lacked the ERR genes and thus ERRs in skeletal muscle. These mice showed profound intolerance to exercise. ERRα and ERRγ appear to be most important for exercise tolerance, with knockout mice for these two genes showing pale muscles under microscopic examination as well as severe exercise intolerance and decreased oxidative capacity. They also showed an inability to switch to lipid (fat) utilization which is critical for endurance exercise

ERRα regulates genes involved in gluconeogenesis (the production of blood sugar from non-carbohydrate energy stores), fatty acid metabolism, and brown adipose tissue thermogenesis. It also regulates cholesterol, glucose, insulin, and triglyceride levels. It is a necessary receptor for responding to physiological and pathological stresses and has been shown to be a target of the statin class of drugs

ERRγ is much like ERRα. It is an important regulator of mitochondrial activity, plays a vital role in gene transcription, and is a major target of bisphenol A. Interestingly, the binding of bisphenol A (BPA) to the ERRγ receptor may be one reason that BPA has been linked to metabolic syndrome as well as cancer. BPA binding to ERRγ likely interferes with its ability to regulate mitochondrial activity leading directly to glucose dysregulation and, eventually, metabolic syndrome. BPA has long been known to be an endocrine disrupter, showing effects on bone strength and sexual development in mice

SLU-PP-332: Research

SLU-PP-332: A Note on Bioavailability

One of the things that makes SLU-PP-332 so important is its ability to reach ERRs throughout the body following injection. This is what allows SLU-PP-332 to be used in in vivo (inside living things) research. While ERR receptor agonists have been developed in the past, most of them were only useful for research in vitro (outside living things) because they were broken down or otherwise incapable of reaching their intended targets. SLU-PP-332 is one of the first compounds to have ERR-binding activity in actual living cells as well as an acceptable safety profile. Additionally, SLU-PP-332 is one of the first ERRα agonists developed. While ERRβ/γ agonists have been relatively easy to design, ERRα agonists have proven elusive. Until the development of SLU-PP-332, no ERRα agonist existed despite that fact that ERRα was the first ERR identified

SLU-PP-332: An Exercise Mimetic

The benefits of physical exercise are myriad. Research indicates that cardiovascular exercise, such as jogging, can enhance weight loss, boost muscle mass and function, increase bone strength, improve cardiovascular well-being, benefit the brain and central nervous system, and even slow down the process of aging . The troubles with exercise, of course, are that not everyone finds it pleasant and making time for it can be difficult. For these, and other reasons, researchers have long searched for compounds that can simulate the benefits of exercise. Sometimes referred to as “exercise in a bottle,” the search for compounds that can mimic the beneficial effects of exercise has led to the discovery of the following compounds.

The peptides above represent just a sampling of the compounds that have been found to mimic some of the benefits of exercise without serious side effects. Prior to SLU-PP-332, very few compounds had been isolated that improved cellular respiration. Cellular respiration is the term used to describe the generation of energy by cells in the body. Most of this energy generation takes place with the mitochondria, which are contained within cells. Mitochondria respond very favorably to exercise, which not only increases the efficiency of these cellular power plants, but increases their numbers within the cell as well. Increases in mitochondria numbers and function are associated with increased basal metabolic rate, improved glucose tolerance, reduced insulin resistance, increased stamina, accelerated growth of small blood vessels, and emergent benefits like improved cardiovascular health.

SLU-PP-332: Caloric Restriction and Aging

Declining renal function occurs with age, but severe loss of renal function is a consequence of disorders like hypertension and metabolic syndrome. It is thought that these conditions lead to inflammation in the kidney and eventual mitochondrial dysfunction, which is the ultimate cause of kidney disease. The kidneys are thus an excellent marker for overall aging and provide a good substrate organ for research into the effects of aging.

Research in human and mouse kidneys has shown that ERRs decrease with age except in individuals who were subjected to life-long calorie restriction. Calorie restriction is one of the few activities with proven anti-aging activity and is known to prolong both lifespan and healthspan. Mice subjected to calorie restriction show improved kidney function when compared to age-matched controls.

Based on this research, it is reasonable to conclude that ERR signaling is a critical factor in long-term well-being and, indeed, researchers have revealed that calorie restriction protects against age-related increases in albumin in the urine, a rise in inflammatory cytokines, and mitochondrial dysfunction. These same benefits are also seen in mice administered SLU-PP-332 that do not undergo calorie restriction.

It is important to note that mitochondrial dysfunction is one of the major hallmarks of aging and is closely interconnected with the process of cellular senescence. Decrease capacity of mitochondria to produce energy resulting in the production of oxygen free radicals which can be extremely damaging to cells. Free radicals lead to cellular damage and this, in turn leads to senescence or to cancer and other serious conditions when senescence is ineffective. The ability to protect mitochondrial function and thus reduce the generation of free radicals is a primary target of anti-aging researchers.

Are There Other ERR Agonists?

SLU-PP-332 is one of three major ERR agonists currently under investigation. The other two are SLU-PP-1072 and SLU-PP-915. Of the two SLU-PP-1072 is the most similar to 332 in that it primarily interacts with the alpha and gamma ERR variants and has been shown to impact mitochondrial function in skeletal muscle. It has been investigated primarily for its ability to induce apoptosis in prostate cancer cells and is being pursued as a potential treatment for prostate cancer

SLU-PP-332: Summary

SLU-PP-332 is an estrogen-related receptor agonist with primary binding proclivities for ERRα and ERRγ. It has more limited binding to ERRβ. Early research has revealed that SLU-PP-332 acts primarily on mitochondria, boosting their capacity to generate energy and reducing oxidative stress as a result. This, in turn, results in increased exercise tolerance and endurance. Additional research has found that SLU-PP-332 can improve heart health, protect the kidneys from the effects of aging, and may help to thwart the pathogenesis of Parkinson’s disease. While research into SLU-PP-332 is just in its infancy, the compound has already shown some remarkable results and has opened up an entirely new area for exploration. SLU-PP-332 is helping scientists to better understand human physiology and will likely lead to the development of a number of therapeutic compounds in the future.

Storage Instructions:

All of our products are manufactured using the Lyophilization (Freeze Drying) process, which ensures that our products remain 100% stable for shipping 3-4 months reconstituted (mixed with bacteriostatic water) to maintain stability. After reconstitution, the peptides will remain stable for up to 30 days.

Lyophilization is a unique dehydration process, also known as cryodesiccation, where the peptides are frozen and then subjected to low pressure. This causes the water in the peptide vial to sublimate directly from solid to gas, leaving behind a stable, crystalline white structure known as lyophilized peptide. The puffy white powder can be stored at room temperature until you're ready to reconstitute it with bacteriostatic water.

Once peptides have been received, it is imperative that they are kept cold and away from light. If the peptides will be used immediately, or in the next several days, weeks or months, short-term refrigeration under 4C (39F) is generally acceptable. Lyophilized peptides are usually stable at room temperatures for several weeks or more, so if they will be utilized within weeks or months such storage is typically adequate.

However, for longer term storage (several months to years) it is more preferable to store peptides in a freezer at -80C (-112F). When storing peptides for months or even years, freezing is optimal in order to preserve the peptide’s stability.

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