What is SLU-PP-332?
SLU-PP-332 is a synthetic fluorinated small molecule studied in research as a pan-agonist of the estrogen-related receptor (ERR) family, comprising ERRα, ERRβ, and ERRγ. It is catalogued under CAS number 2155854-26-3 with a molecular formula of C₂₀H₁₈F₃N₃O₂ and a molecular weight of 393.37 g/mol. Supplied as a lyophilized powder, it is intended strictly for laboratory research purposes and is not for human or animal use.
SLU-PP-332 was developed in academic research — the "SLU" designation reflects its origin at Saint Louis University — specifically to address the challenge of pharmacologically activating the ERR family with a single compound. Prior to SLU-PP-332, ERR agonists with activity across all three receptors at comparable potency were not readily available as research tools. The compound's pan-agonist profile across ERRα, ERRβ, and ERRγ makes it useful for studying the ERR family as a functional unit rather than requiring parallel experiments with receptor-subtype-selective tools.
What is the molecular structure of SLU-PP-332?
SLU-PP-332 has a molecular weight of 393.37 g/mol and the molecular formula C₂₀H₁₈F₃N₃O₂. Its structure features a trifluoromethyl (CF₃) group — the source of the three fluorine atoms in the formula — which is a common structural motif in synthetic small-molecule medicinal and research chemistry. The CF₃ group contributes to metabolic stability in cell-model systems by resisting cytochrome P450-mediated oxidative metabolism at that position. It also modulates the compound's lipophilicity and binding affinity at target sites through electronic and steric effects.
The core scaffold contains an aromatic heterocycle with nitrogen atoms (three in total, per the formula), which positions SLU-PP-332 as a synthetic ligand designed to bind the ligand-binding domain (LBD) of ERR receptors. Unlike the ERR family's natural endogenous ligand situation — ERRs are classified as constitutively active orphan nuclear receptors, and no physiological endogenous ligand that activates them through the canonical LBD mechanism has been conclusively established — SLU-PP-332 acts as an exogenous synthetic agonist that drives receptor activity through LBD engagement.
Compared to larger peptide-based metabolic research compounds, SLU-PP-332's molecular weight of 393.37 g/mol is consistent with the small-molecule range. It is stored at −20°C in lyophilized form and characterized to a purity specification of 99.1% by HPLC.
What are the estrogen-related receptors?
The estrogen-related receptors (ERRα, ERRβ, ERRγ) are nuclear receptors in the nuclear receptor superfamily, encoded by the genes ESRRA, ESRRB, and ESRRG, respectively. They are structurally related to estrogen receptors (ERα and ERβ) but are functionally distinct: they do not bind estrogens, and their regulation, transcriptional targets, and tissue distribution differ substantially from the classical estrogen receptors.
ERRs are classified as constitutively active orphan nuclear receptors. "Orphan" refers to the fact that no clearly established physiological endogenous ligand for the LBD has been identified for the ERR family members. "Constitutively active" means that in the absence of a ligand, these receptors exhibit measurable transcriptional activity — unlike most nuclear receptors, which require ligand binding to adopt an active conformation. The basis for ERR constitutive activity lies in the orientation of helix 12 (the activation function 2, or AF-2 helix) within the ligand-binding domain, which adopts an active conformation independent of LBD occupancy.
ERRs regulate gene expression by binding to ERR response elements (ERREs) in the promoters and enhancers of target genes, both as monomers and homodimers. Their transcriptional activity is modulated by coactivators, particularly PGC-1α and PGC-1β, which interact with the AF-2 domain of the receptors and dramatically amplify their transcriptional output. The ERR–PGC-1α coactivator complex is a well-characterized axis in published metabolic pathway research.
The three ERR subtypes share conserved DNA-binding and ligand-binding domains but differ in tissue expression patterns and transcriptional target gene sets, which is why pan-agonism — activating all three — is mechanistically distinct from subtype-selective pharmacology.
How does SLU-PP-332 interact with ERRα, ERRβ, and ERRγ?
SLU-PP-332 is described in the research literature as a pan-agonist of the ERR family, meaning it demonstrates agonist activity at ERRα, ERRβ, and ERRγ. The mechanism of agonism at constitutively active nuclear receptors like the ERRs involves stabilization of the active receptor conformation — in particular, stabilizing the AF-2 helix in the position that enables coactivator recruitment — rather than switching an otherwise inactive receptor to an active state.
In practice, SLU-PP-332 binding to the ERR LBD is studied for its ability to increase the receptor's transcriptional activity above the constitutive baseline by enhancing coactivator association. Published research on SLU-PP-332 characterizes its binding affinity and functional agonism at each of the three ERR subtypes. The compound shows activity across all three, which distinguishes it from earlier ERR modulators with limited subtype coverage.
In cell-based reporter assays — a standard format for characterizing nuclear receptor pharmacology — SLU-PP-332 produces concentration-response relationships at ERRα, ERRβ, and ERRγ consistent with agonism at each receptor subtype. Concentration-response profiling in these systems is the primary method for characterizing potency and relative activity across subtypes.
What downstream transcriptional signaling is studied in SLU-PP-332 research?
The ERR receptors, in complex with PGC-1 coactivators, regulate gene programs associated with mitochondrial function and oxidative metabolism at the transcriptional level. Published research characterizes the downstream transcriptional targets of ERR–PGC-1α complexes as including genes involved in:
Mitochondrial biogenesis. ERRα and ERRγ, in complex with PGC-1α, regulate transcription of genes encoding components of the electron transport chain, TCA cycle enzymes, and mitochondrial ribosomal proteins. Research models examining SLU-PP-332 have used mitochondrial gene expression panels as downstream readouts of ERR transcriptional activity.
Fatty acid oxidation gene regulation. ERRs regulate expression of genes encoding enzymes in the fatty acid β-oxidation pathway at the transcriptional level. In research models, SLU-PP-332 has been used to examine how ERR agonism influences the transcriptional output of these gene programs in cell-based systems. This is strictly a mechanistic/transcriptional observation — the characterization is of gene expression levels in model systems, not of organismal metabolic outcomes.
OXPHOS gene regulation. Oxidative phosphorylation (OXPHOS) complex subunit genes are among the transcriptional targets of the ERR–PGC-1α axis in published research. SLU-PP-332-mediated ERR activation is studied in cell models for its effects on OXPHOS gene expression as a readout of the pathway's transcriptional activity.
Valitec makes no outcome claims regarding any of these signaling relationships. The downstream effects described here are the mechanistic characterizations published in academic research using SLU-PP-332 in cell model systems — not assertions about what the compound does in living systems outside controlled in vitro research.
How does SLU-PP-332 differ from AMPK-targeting compounds like AICAR?
AICAR and SLU-PP-332 are both classified as metabolic research compounds, but they act through mechanistically unrelated pathways and at different points in cellular signaling hierarchy.
| Property | AICAR | SLU-PP-332 |
|---|---|---|
| Compound class | Nucleotide analog | Fluorinated small molecule |
| Primary target | AMPK (via γ subunit ZMP-mediated activation) | ERRα, ERRβ, ERRγ (nuclear receptor LBD) |
| Mechanism layer | Cytoplasmic kinase signaling | Nuclear transcriptional regulation |
| Downstream readouts | pACC, pThr172-AMPK, mTORC1 pathway | ERR target gene expression, OXPHOS gene panels |
| Speed of effect in models | Post-translational (minutes to hours) | Transcriptional (hours to days) |
| Purity (Valitec specification) | 99.1% | 99.1% |
| Molecular weight | 258.23 g/mol | 393.37 g/mol |
The distinctions matter for research design. AMPK activation (via AICAR's ZMP intermediate) is a post-translational kinase signaling event that operates on existing proteins through phosphorylation. ERR agonism (via SLU-PP-332) operates at the transcriptional level through nuclear receptor–coactivator complex formation, producing changes in gene expression over longer timescales. The two pathways do intersect — PGC-1α is a downstream transcriptional target influenced by both AMPK activity and ERR signaling — but the mechanistic entry points are distinct.
Researchers studying the relationship between kinase-level energy sensing (AMPK) and transcriptional metabolic regulation (ERR) may use both compounds in parallel or sequential experimental designs to dissect the relative contributions of each pathway. For the AICAR research overview, see AICAR: AMPK Activation and Metabolic Research.
What is known about SLU-PP-332's stability and handling in research?
SLU-PP-332 is supplied as a lyophilized powder characterized to a purity of 99.1% by HPLC with identity confirmation by mass spectrometry. Storage is at −20°C. The trifluoromethyl group in the structure contributes metabolic stability in cell-model systems, but the lyophilized compound should be protected from moisture exposure in storage, consistent with standard laboratory handling practices for small-molecule research materials.
SLU-PP-332 demonstrates cell permeability consistent with its molecular weight and lipophilicity, making it accessible to nuclear compartments in standard cell culture research formats. The specific concentration-response ranges and handling protocols used in published research vary by experimental system; researchers determine these parameters independently in accordance with their experimental design, applicable laboratory regulations, and standard practices.
As with all research compounds in the Valitec catalog, Valitec does not provide preparation, concentration, or handling guidance. Researchers apply their own protocols.
How does Valitec source SLU-PP-332?
Valitec supplies SLU-PP-332 as a research-grade compound held to a minimum purity specification of 99% or higher by HPLC, with batch-specific identity confirmation by mass spectrometry. Each order ships with a batch-specific Certificate of Analysis including the chromatogram and MS data. Shipments are cold-chain packaged as standard. For a detailed breakdown of what COA documentation covers and what it does not, see research compound sourcing documentation.
Specifications, available sizes, and ordering information are at the SLU-PP-332 product page. All material is supplied for laboratory research use only.
SLU-PP-332 is a research chemical intended for laboratory and scientific research purposes only. It is not a drug, supplement, or food product, and is not intended to diagnose, treat, cure, or prevent any disease. Valitec Peptides does not supply products for human or animal use. Researchers are responsible for compliance with all applicable local, state, and federal regulations governing the purchase and use of research materials.