SLU-PP-332 — Research, Dosing & Price Guide

SLU-PP-332 is a small-molecule agonist of the estrogen-related receptor (ERR) family, particularly ERRα, ERRβ, and ERRγ. Dubbed an 'exercise mimetic,' it activates the same transcriptional programs induced by endurance exercise — mitochondrial biogenesis, fatty acid oxidation, and oxidative muscle fiber gene expression. In preclinical studies, it dramatically improved exercise endurance and fatigue resistance without physical training.

SLU-PP-332 activates the estrogen-related receptors (ERRs), a family of orphan nuclear receptors that serve as master regulators of energy metabolism. Despite their name, ERRs do not bind estrogen — they regulate genes involved in mitochondrial biogenesis (PGC-1α, NRF1, TFAM), oxidative phosphorylation, fatty acid oxidation (CPT1, MCAD, VLCAD), and the tricarboxylic acid cycle. ERRα is the predominant isoform in skeletal muscle, heart, and brown adipose tissue. By activating ERRs, SLU-PP-332 upregulates the transcription of hundreds of metabolic genes simultaneously, effectively reprogramming muscle fibers toward a more oxidative (slow-twitch) phenotype. This increases mitochondrial density, enhances lipid utilization over glucose, and improves fatigue resistance. The compound also increases VEGF expression, promoting angiogenesis in skeletal muscle, and activates UCP-1 in brown adipose tissue, enhancing thermogenesis.

• A 2023 study in ACS Chemical Biology from Washington University showed SLU-PP-332 increased treadmill running endurance by 40–70% in sedentary mice
• Treated mice showed significantly increased expression of oxidative phosphorylation genes and mitochondrial biogenesis markers
• Muscle fiber type analysis revealed a shift from glycolytic (type IIb) to oxidative (type I/IIa) fibers
• The compound reduced muscle fatigue and improved lactate clearance during exhaustive exercise
• ERR activation by SLU-PP-332 also reduced muscle damage markers after exhaustive exercise
• Developed by Thomas Bhurke's group at Washington University in St. Louis, published in 2023

• Preclinical dose: 25–50 mg/kg administered intraperitoneally in mice (not directly translatable to humans)
• No established human dosing protocol — compound is in preclinical research phase
• Research protocols typically involve daily administration for 4–8 weeks
• Oral bioavailability has been demonstrated in rodent models
• May be combined with physical exercise for potentially synergistic effects on endurance
• Human-equivalent dose estimation suggests 2–4 mg/kg orally, but this is speculative

Known Side Effects

• No human safety data available — all data is from preclinical models
• Rodent studies have not reported significant toxicity at therapeutic doses
• Theoretical concern about cardiac effects given ERR expression in heart tissue
• Potential hormonal effects due to structural similarity to estrogen-related receptors, though ERRs do not bind estrogen
• Unknown long-term effects on muscle fiber composition and metabolic flexibility

Safety Profile

SLU-PP-332 is an early-stage research compound with no human clinical data. Preclinical toxicology in rodents has not revealed major organ toxicity at effective doses, but comprehensive safety studies have not been completed. The ERR receptor family is expressed in multiple tissues including heart, liver, kidney, and brain, raising the possibility of off-target metabolic effects. Long-term consequences of forced mitochondrial biogenesis and fiber-type switching are unknown. This compound should be considered strictly experimental. Not recommended for human use until Phase I safety data becomes available.

No human experience data exists. In preclinical models, effects on exercise endurance are observed within 2–4 weeks of daily administration. Mitochondrial biogenesis and fiber-type changes occur gradually over weeks. If human effects mirror rodent data, one might expect improved exercise endurance, reduced fatigue, enhanced fat utilization during exercise, and improved recovery — essentially mimicking the adaptations of a structured endurance training program. However, without human data, all expectations are speculative.

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