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SLU-PP-332: A (relatively) Comprehensive Overview
SLU-PP-332 is a small molecule that acts as a potent, non-selective agonist of estrogen-related receptors (ERRs), particularly ERRα. Developed at Saint Louis University School of Medicine, it has garnered attention for its potential applications in metabolic health, exercise mimetics, and bodybuilding.
Mechanism of ActionAs an ERRα agonist, SLU-PP-332 enhances mitochondrial activity and energy metabolism. It binds to the ERRα receptor, stabilizing its active conformation and enhancing its interaction with coactivator proteins, particularly PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). This activation leads to:
- Upregulation of mitochondrial biogenesis through increased expression of TFAM (mitochondrial transcription factor A).
-Enhanced expression of genes involved in oxidative phosphorylation (OXPHOS).
-Increased fatty acid uptake and β-oxidation through regulation of CPT1 (carnitine palmitoyltransferase 1) and MCAD (medium- chain acyl-CoA dehydrogenase).
-Stimulation of AMPK (AMP-activated protein kinase) signaling, mimicking energy-deprived cellular states.
These effects collectively improve cellular energy production, fat oxidation, and overall metabolic efficiency.
Pharmacology and PharmacokineticsAbsorption: Oral bioavailability has not been established. In fact studies indicate it will need to be altered to allow for oral administration vs injection or IP administration. Here is a quote from a relevant study= "The next step is to improve its structure and make it into a medication candidate, ideally so that it may be given as a tablet rather than an injection"
There is no evidence this can be administered orally and while lots of companies seem to be selling oral capsules the chance is high that these are either completely fake and lacking SLUpp332 or inert as MCG doses orally are likely not viable orally. In addition it appears that SLUPP332 degrades quickly in solution. Multiple sources indicate that even when stored at -80c it may be viable for several months while at -20c it remains viable for about 30 days. At room temperature it degrades rapidly within around 48 hours. This means that a liquid oral would be inert by the time it reached any customer. As a result Black Lion Research has developed a sublingual version as this compound is a prime candidate for subulingual administration. This means that our sublingual tablets are likely the only viable option presently available.
Distribution: Widely distributed to metabolically active tissues including liver, skeletal muscle, and adipose tissue, with high mitochondrial tropism.
Metabolism: Primarily metabolized by hepatic CYP450 enzymes, with phase II glucuronidation as a secondary pathway.
Elimination: Predominantly excreted via biliary/fecal routes with a plasma half-life of approximately 8-10 hours in rodents.
Blood-Brain Barrier: Limited penetration across the blood-brain barrier (<5% of plasma levels).
Benefits1. Exercise Mimetic Effects
SLU-PP-332 mimics the physiological effects of exercise, providing benefits such as:
Increased mitochondrial density in skeletal muscle.
Enhanced expression of GLUT4 glucose transporters in muscle tissue.
Improved muscular endurance and running capacity.
Reprogramming of muscle fiber type composition toward more oxidative phenotypes.
Increased vascular density in skeletal muscle.
Enhanced cardiac efficiency through improved mitochondrial function.
In another paper published in March, the researchers reported that they had observed that the compound allowed normal-weight mice to run for 70% longer and 45% further than mice not receiving SLU-PP-332.
2. Fat Loss and Metabolic Health
Studies in animal models have shown that SLU-PP-332 improves insulin sensitivity and reduces adiposity, while anecdotal evidence shows that SLU-PP-332 is exceptional as a fat loss agent. When administered to diet-induced obese mice, SLU-PP-332 produced:
18-24% reduction in body weight.
30-35% decrease in white adipose tissue mass.
40% improvement in glucose tolerance.
25-30% decrease in fasting insulin levels.
Significant reduction in hepatic steatosis and inflammation.
3. Mitochondrial Health and Aging
SLU-PP-332 has been studied for its role in reversing mitochondrial dysfunction and inflammation in aging tissues. In aged rodent models, SLU-PP-332 demonstrated:
Restoration of mitochondrial respiration rates in kidney and liver tissues.
Reduction in age-associated inflammation markers (IL-6, TNF-α).
Decreased oxidative damage to mitochondrial DNA.
Improved autophagy and mitophagy.
Attenuation of fibrotic tissue changes in kidneys and heart.
4. Muscle Mass Maintenance:
It may help preserve muscle mass during weight loss or aging, which are situations where muscle loss is a concern.
Improved insulin sensitivity.
Improved Muscle mitochondrial function.
Improved endurance.
5. Cardioprotective Effects:
Preservation of Cardiac Contractility: SLU-PP-332 has shown promise in preserving heart function after ischemic events (reduced blood flow to the heart).
Reduced Cardiomyocyte Apoptosis: It can help prevent the death of heart muscle cells.
Improved Myocardial Energetics: The compound enhances fatty acid oxidation in the heart, leading to improved energy production.
SLU-PP-332 has demonstrated the ability to improve heart function in animal models of heart failure by enhancing fatty acid oxidation and mitochondrial metabolism. It can also reduce fibrosis in the heart.
Research and ApplicationsSLU-PP-332 has been tested in several pre clinical studies, including its ability to:
Improve metabolic syndrome by enhancing mitochondrial efficiency.
Induce exercise-mimetic effects in muscle tissue.
Reverse age-related mitochondrial dysfunction.
Current development status includes advanced toxicology studies in multiple species, with safety profiles generally well-tolerated in rodent and canine models at therapeutic doses. Oral and Extended-release formulations are under development to optimize pharmacokinetics. SLU-PP-332 has been tested up to 1000mg in rodent models.
