What is SLU-PP-332?
SLU-PP-332 is a small-molecule agonist of estrogen-related receptor alpha (ERRα), an orphan nuclear receptor that transcriptionally regulates genes involved in mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation. ERRα is constitutively active in tissues with high energy demands (skeletal muscle, heart, brown fat) and cooperates with PGC-1α to drive expression of oxidative metabolism gene programs. SLU-PP-332 was developed at Saint Louis University and has been investigated as an “exercise mimetic” — a compound that activates transcriptional programs normally induced by endurance exercise. In preclinical models, researchers observed that SLU-PP-332 treatment was associated with increased expression of type I (slow-twitch, oxidative) muscle fiber genes and enhanced running endurance without exercise training. The compound represents a pharmacological approach to activating the ERRα/PGC-1α transcriptional axis.
Mechanism of Action
SLU-PP-332 has been investigated for its agonist binding to ERRα, stabilizing the receptor in an active conformation that enhances recruitment of PGC-1α and other co-activators to ERRα target gene promoters. Researchers observed that ERRα activation by SLU-PP-332 increases transcription of OXPHOS genes (Complexes I-V), fatty acid oxidation enzymes (CPT1, MCAD), and mitochondrial biogenesis factors (TFAM, NRF1). Studies suggest that this transcriptional reprogramming shifts muscle fiber type composition toward a more oxidative phenotype, with increased expression of type I fiber markers (myosin heavy chain I, myoglobin) and enhanced mitochondrial content. In preclinical models, researchers observed that SLU-PP-332 administration was associated with improved running endurance, increased VO2max, and enhanced fatigue resistance. The compound also upregulated expression of genes involved in reactive oxygen species detoxification, consistent with the enhanced antioxidant capacity observed in endurance-trained muscle.
Published Research
Exercise Mimetic Properties
Kim et al. (2023) investigated SLU-PP-332 in mice and observed increased oxidative muscle fiber gene expression and enhanced running endurance without exercise training, establishing the compound as an ERRα-mediated exercise mimetic [1].
ERRα Biology
Giguère (2008) reviewed ERRα’s role in energy metabolism, describing how this nuclear receptor coordinates mitochondrial biogenesis and oxidative phosphorylation in high-energy-demand tissues [2].
ERR Agonist Development
Patch et al. (2011) described the development of ERR agonists and characterized their effects on metabolic gene expression in cellular models [3].
Product Specifications
| Product | SLU-PP-332 Lyophilized Powder |
|---|---|
| Available Sizes | 100mg x 120 Capsules, 100mg x 30 Capsules, 1mg/ML 30 ML, .5mg/ML 30 ML, 1mg x 30 Capsules |
| Purity | ≥99% (HPLC verified) |
| CAS Number | 2098629-16-0 |
| Molecular Formula | C₂₂H₁₉N₃O₃ |
| Molecular Weight | 373.40 g/mol |
| Appearance | White lyophilized powder in glass vial |
| Storage | Store at -20°C desiccated. Protect from light and moisture. |
| Testing | Third-party tested — Certificate of Analysis available |
Frequently Asked Questions
SLU-PP-332 is a small-molecule agonist of ERRu03b1 (estrogen-related receptor alpha) studied as an exercise mimetic that activates oxidative metabolism gene programs.
The CAS registry number for SLU-PP-332 is 2098629-16-0.
No, SLU-PP-332 is a small molecule. It is a nuclear receptor agonist that modulates gene transcription through ERRu03b1.
ERRu03b1 is an orphan nuclear receptor that regulates mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation genes. It cooperates with PGC-1u03b1 in tissues with high energy demands.
Store at -20°C desiccated, protected from light and moisture.
References
- Kim SH, et al. ERR agonist SLU-PP-332 promotes exercise-like changes in muscle. Research presented 2023.
- Giguère V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev. 2008;29(6):677-696. PMID: 18664618
- Patch RJ, et al. Identification of diaryl ether-based ligands for estrogen-related receptor α as potential antidiabetic agents. J Med Chem. 2011;54(3):788-808. PMID: 21218783
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