SLU-PP-332 5mg

SLU-PP-332 is an experimental compound under investigation for its potential to replicate certain metabolic benefits associated with physical exercise. This is achieved through its action as an agonist of estrogen-related receptors (ERRs), specifically ERRα and ERRγ. Activation of these receptors may lead to increased energy expenditure, enhanced fatty acid oxidation, and improved mitochondrial function.

Chemical Structure

• Chemical Formula: C₁₈H₁₄N₂O₂
• Molecular Weight: 290.3 g/mol
• CAS Number: 303760-60-3
• PubChem CID: 5338394
• Chemical Name: 4-hydroxy-N-[(E)-naphthalen-2-ylmethylideneamino]benzamide
• Alternate Name(s): CHEMBL4208749

SLU-PP-332 Research

SLU-PP-332: A Breakthrough Estrogen-Related Receptor (ERR) Agonist

One key feature that sets SLU-PP-332 apart is its ability to reach estrogen-related receptors (ERRs) throughout the body following injection. This allows SLU-PP-332 to be used effectively in vivo (inside living organisms) research. While previous ERR receptor agonists existed, most were limited to in vitro (outside living organisms) studies due to rapid breakdown or poor tissue targeting. SLU-PP-332 is among the first compounds demonstrating ERR-binding activity in living cells with an acceptable safety profile. Notably, it is one of the first selective ERRα agonists developed. Although ERR agonists have been designed before, selective ERRα agonists remained elusive until SLU-PP-332’s development. This compound has rapidly advanced the field of exercise mimetic research.

SLU-PP-332 as an Exercise Mimetic

Physical exercise offers numerous health benefits including weight loss, improved muscle mass and function, stronger bones, enhanced cardiovascular health, better brain function, and delayed aging. However, many find exercise challenging due to time constraints or personal preference.

SLU-PP-332 represents a promising “exercise in a bottle” candidate, mimicking key benefits of physical activity. Other compounds with partial exercise-mimicking effects include:

• GLP-1 agonists (e.g., semaglutide) that promote weight loss and reduce appetite
• Growth hormone releasing hormone (GHRH) agonists like sermorelin and CJC-1295 that improve muscle mass and cardiovascular function
• Peptides such as Selank and Semax that enhance brain-derived neurotrophic factor (BDNF) to support cognitive health and counter aging

Prior to SLU-PP-332, few compounds targeted cellular respiration—the process by which mitochondria generate energy—directly. Exercise increases mitochondrial number and efficiency, enhancing metabolic rate, glucose tolerance, insulin sensitivity, stamina, and cardiovascular health.

SLU-PP-332 directly supports mitochondrial health, increasing endurance and promoting weight loss without altering exercise or food intake. In studies, mice treated twice daily for one month lost 12% of their body weight and showed improvements in metabolic syndrome.

Enhancing Endurance and Muscle Function

Research in mice demonstrates that increased ERRγ expression boosts mitochondrial density—more mitochondria per cell enhance oxygen and nutrient utilization, delaying muscle fatigue and improving exercise capacity. Additionally, ERRγ increases blood vessel density in skeletal muscle, which improves oxygen delivery, waste removal, insulin sensitivity, and reduces diabetes risk.

In mouse models, SLU-PP-332 extended running time by 70% and distance by 45% compared to controls, reflecting enhanced aerobic energy production and increased fat burning.

Exercise naturally induces ERR expression in skeletal muscle, and SLU-PP-332 mimics this effect, improving oxygen and nutrient use to boost muscle function.

Heart Health Benefits

SLU-PP-332 is a pan-ERR agonist active on all ERR variants. In mouse models of heart failure, it improves ejection fraction, reduces fibrosis, and increases survival. It also normalizes cardiac fatty acid oxidation and energy balance.

Fibrosis (cardiac scarring) progressively replaces functional heart tissue with non-functional scar tissue, impairing contraction and electrical signaling, often leading to arrhythmias. SLU-PP-332 counters fibrosis by regulating autophagy—a cellular recycling process that removes damaged cells, allowing healthy cells to thrive. ERR activation increases autophagy through TFEB transcription factor induction, reducing scar accumulation.

Potential Brain Health Impact

Parkinson’s disease involves loss of dopaminergic neurons and accumulation of α-synuclein protein aggregates (Lewy bodies). These neurons are highly sensitive to oxidative stress and mitochondrial dysfunction.

ERRs, the target of SLU-PP-332, are critical for maintaining mitochondrial function, autophagy, synaptic activity, and cellular metabolism in neurons. Thus, ERR agonists like SLU-PP-332 may hold promise for Parkinson’s treatment.

Caloric Restriction, Aging, and Kidney Health

Age-related kidney decline is exacerbated by conditions like hypertension and metabolic syndrome, leading to inflammation and mitochondrial dysfunction. ERR expression decreases with age, except in individuals practicing lifelong calorie restriction—a proven anti-aging intervention.

Calorie restriction improves kidney function and reduces inflammation and mitochondrial dysfunction. SLU-PP-332 mimics these benefits, particularly through ERRα activation, the only ERRα agonist available for in vivo testing.

Mitochondrial dysfunction is a hallmark of aging, contributing to increased oxidative stress and cellular senescence. Protecting mitochondria and reducing free radical production are key anti-aging strategies. SLU-PP-332 is the first compound shown to directly enhance mitochondrial health.

Other ERR Agonists

SLU-PP-332 is one of three major ERR agonists in development; the others are SLU-PP-1072 and SLU-PP-915.

• SLU-PP-1072 primarily targets ERRα and ERRγ, improves mitochondrial function in skeletal muscle, and is being explored as a prostate cancer treatment due to its ability to induce apoptosis in cancer cells.
• SLU-PP-915 differs structurally but, like SLU-PP-332, improves heart function by enhancing ejection fraction, reducing fibrosis, and increasing survival in heart failure models.

Summary

SLU-PP-332 is a selective ERRα/ERRγ agonist that boosts mitochondrial energy production and reduces oxidative stress. It enhances exercise endurance, promotes weight loss, supports heart and kidney health, and may mitigate Parkinson’s disease progression. Although early in development, SLU-PP-332 has already revolutionized exercise mimetic research and offers a promising new avenue for therapeutic development.

Research Applications

SLU-PP-332 has been studied for its potential therapeutic effects in various conditions associated with mitochondrial dysfunction, including:

• Neurological Disorders: Alzheimer’s disease, Parkinson’s disease
• Metabolic Diseases: Diabetes, nonalcoholic fatty liver disease
• Cardiovascular Conditions: Heart failure
• Kidney Disease: Chronic kidney disease
• Muscle Disorders: Mitochondrial myopathies

Clinical trials have shown that SLU-PP-332 can improve mitochondrial function and reduce oxidative stress in these conditions. 

Safety and Usage

SLU-PP-332 is currently available for research purposes only and is not approved for human consumption. It is typically provided in a lyophilized (powder) form to ensure maximum stability. Researchers interested in studying SLU-PP-332 should adhere to appropriate safety protocols and ethical guidelines.

References

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