SLU-PP-332 is a synthetic benzohydrazide-class compound developed at Saint Louis University as an agonist of the three estrogen-related receptors (ERRα, ERRβ and ERRγ). It is a small molecule rather than a peptide. Its research interest lies in its use as a chemical probe of ERR-driven transcription, a nuclear-receptor program that regulates genes involved in mitochondrial function and oxidative metabolism. The published data on SLU-PP-332 come from in-vitro and animal research. This overview covers its chemical classification, receptor pharmacology, published research context, analytical characterization and laboratory handling.
Chemical class: benzohydrazide derivative. Primary target: ERRα (EC50 ≈ 98 nM); ERRβ (EC50 ≈ 230 nM); ERRγ (EC50 ≈ 430 nM). Classification: synthetic pan-ERR nuclear receptor agonist.
Important classification note: SLU-PP-332 is a small molecule, not a peptide in the chemical sense. It is listed alongside research peptides for catalog convenience, but its chemistry, solubility and handling are those of a small organic molecule.
The estrogen-related receptors are orphan nuclear receptors. Despite sequence similarity to the estrogen receptors, they do not bind estradiol and show substantial constitutive activity. They regulate transcription of genes involved in mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation, largely in partnership with the transcriptional coactivators PGC-1α and PGC-1β.
SLU-PP-332 binds the ligand-binding domain of ERRα, ERRβ and ERRγ, stabilizing an active receptor conformation and enhancing coactivator recruitment. In cell-based assays this is read out as increased expression of ERR target genes such as CPT1B and COX4I1 and of other genes of mitochondrial respiration.
Subtype contributions differ by cell type: ERRα is the dominant isoform in many cultured cell models, while ERRγ is prominent in cardiac-derived cells. Selective ERR inverse agonists and receptor knockdown are commonly used alongside SLU-PP-332 to attribute an effect to an individual subtype.
Billon et al. (2023, PMID: 36988910) described the pharmacology of SLU-PP-332 as an ERR agonist and examined ERR target-gene expression and mitochondrial respiration in C2C12 myoblast-derived cells and in mouse models.
Billon et al. (2024, PMC10801787) extended this work to additional mouse models, measuring ERR-dependent gene expression together with markers of mitochondrial and lipid metabolism.
Further preclinical reports published in 2024 examined pan-ERR agonism in cardiac-derived cells and rodent cardiac tissue, focusing on myocardial fatty acid oxidation and mitochondrial gene expression.
SLU-PP-332 is used in: nuclear receptor pharmacology, studies of ERR and PGC-1α transcriptional networks, mitochondrial biogenesis research in cultured cells, and comparative pharmacology against other nuclear-receptor modulators.
It also serves as a chemical probe to separate PGC-1α-dependent from PGC-1α-independent ERR signaling, and as a reference agonist when screening new ERR ligands in reporter-gene and coactivator-recruitment assays. These applications make it a useful tool for basic transcriptional biology research.
As a small molecule, SLU-PP-332 is characterized by reverse-phase HPLC for purity, mass spectrometry for identity and, where available, NMR spectroscopy to confirm structure. Its aqueous solubility is limited.
ERR agonists are usually evaluated in reporter-gene assays in which an ERR response element drives luciferase expression, in coactivator-recruitment assays (for example TR-FRET) using purified ligand-binding domains, and by qPCR of endogenous target genes. Because the ERRs are constitutively active, the assay window for an agonist is smaller than for a classical ligand-activated receptor, so concentration–response curves are typically run in replicate with an inverse agonist as a reference compound.
Cytotoxicity counter-screens help confirm that transcriptional readouts reflect receptor activity rather than changes in cell viability.
SLU-PP-332 is not approved by the FDA for human or veterinary use. Material sold as a research chemical is supplied for in-vitro laboratory research and identification purposes only.
Form: lyophilized powder or solid. Storage: −20°C, desiccated and protected from light. Keep containers tightly sealed to limit moisture uptake.
For research use only. Not for human consumption.
No. Although it is listed alongside peptides, SLU-PP-332 is a synthetic small molecule (benzohydrazide class). It is not a peptide in the chemical sense.
ERRα, ERRβ and ERRγ are orphan nuclear receptors related in sequence to the estrogen receptors but not activated by estradiol. They regulate genes of mitochondrial function and oxidative metabolism together with the coactivator PGC-1α.
Published SLU-PP-332 data come from in-vitro and animal research: ERR target-gene expression, coactivator recruitment and mitochondrial respiration in cultured cells, and ERR-dependent gene expression in mouse models.
SLU-PP-332 is a pan-ERR agonist that is most potent at ERRα (EC50 ≈98 nM), followed by ERRβ (≈230 nM) and ERRγ (≈430 nM).