Molecule guides
SLU-PP-332: An ERR Pan-Agonist Probe for Transcriptional Metabolic Research
A non-peptide nuclear receptor agonist whose effects show up in gene expression rather than signalling — what it targets, why timing dominates the design, and how to stock it.
A non-peptide compound of 290.27 g/mol, SLU-PP-332 acts as a pan-agonist at the estrogen-related receptors — ERR alpha, beta and gamma — and is studied as a probe for exercise mimicry. It is neither a peptide nor a hormone, and despite what its target family is called it does not bind the estrogen receptor. Its appeal is that it works on a transcriptional programme rather than a cell-surface receptor, which sets it mechanistically apart from nearly everything else in a metabolic peptide catalogue. Our SLU-PP-332 for laboratory research ships as lyophilized powder in sealed vials, for laboratory use only.
Defining SLU-PP-332
Orphan nuclear receptors, the ERRs are transcription factors whose name comes from sequence similarity to the estrogen receptor rather than from binding estrogen. That they are orphans means no endogenous ligand has been identified for them. Their target genes govern the building of new mitochondria, oxidative phosphorylation and fatty-acid oxidation, and ERR alpha in particular collaborates with PGC-1 alpha, the transcriptional hub that exercise switches on in skeletal muscle.
SLU-PP-332 emerged as a synthetic agonist active at all three ERR isoforms. Because it operates intracellularly on transcription rather than at the cell surface, its effects unfold over hours and days as expression changes, not within minutes as a signalling event would — and that distinction dictates how any experiment using it has to be built.
Origin and structure
- Class of compound. A non-peptide small-molecule agonist of a nuclear receptor, arising from a synthetic screening series rather than from a natural product.
- Identifiers. Molecular weight 290.27 g/mol; CAS 2098486-97-2.
- Target. All three isoforms — ERR alpha, ERR beta and ERR gamma — making it a pan-agonist rather than an isoform-selective probe.
- Solubility. Concentrated stocks go into DMSO before dilution into assay medium or buffer. Unlike a charged molecule such as 5-Amino-1MQ it does not dissolve freely in water, and that limits how it can be prepared.
The proposed mechanism
A nuclear receptor binds response elements in the promoters of its target genes and pulls in coactivator complexes that drive transcription. With the ERRs, agonism is reported to raise expression across the oxidative programme: biogenesis of mitochondria, components of the electron transport chain, and fatty-acid oxidation enzymes. Since endurance training induces broadly this same programme through PGC-1 alpha, compounds acting here are called exercise mimetics in the literature — a term capturing a transcriptional resemblance, not equivalence to exercise itself.
In studies before the clinic, SLU-PP-332 has been reported to raise mitochondrial function and oxidative capacity in muscle cells, while rodent work describes greater energy expenditure and improved running endurance. For mechanistic purposes, pan-agonism is a real constraint: the three isoforms differ in tissue distribution and partly in target genes, so an effect cannot be attributed to one of them without an isoform-selective comparator or a knockdown arm. Anyone asking which ERR does what should build that control in from the outset.
The timing point is worth stressing, because it is where badly designed experiments with this compound usually fail. An agonist of a transcription factor produces its effect by altering gene expression, which requires transcription, then translation, and — for mitochondrial biogenesis — the assembly of new organelles. Nothing will appear in a reading taken at thirty minutes; the reported effects emerge between roughly twenty-four and seventy-two hours. By the same logic, the right positive control is not some other metabolic compound but a known inducer of the same programme, and the right negative control accounts for solvent, since DMSO at working concentrations demonstrably affects mitochondrial readouts in certain cell types.
What has been studied
- Reporter and receptor assays. ERR-driven luciferase reporters and coactivator recruitment assays defining agonist activity and potency at each isoform.
- Cell work. Myotube and muscle cell cultures assessing mitochondrial content, oxygen consumption rate and oxidative gene expression.
- Rodent work. Indirect calorimetry for energy expenditure, exercise capacity tests, body composition in diet-induced obesity models, and cardiac tissue studies, ERR signalling being active there too.
- Human evidence. None whatsoever — no clinical trial programme, no published human pharmacokinetics, no human safety data. Our specification sheet says so plainly: cell culture and rodent studies only.
The small-molecule metabolic tools in this range are compared in 5-Amino-1MQ against SLU-PP-332 and in the energy and mitochondria research overview.
Pharmacokinetics is the second limitation the literature acknowledges openly. Compounds from this series are described as giving short exposure and only modest oral availability in rodents, which is why much of the animal work that has been published depends on frequent administration to keep the transcriptional signal going. The consequence for a laboratory is that a negative in vivo finding may indicate too little exposure rather than no activity, and that pharmacokinetic confirmation belongs in the in vivo design rather than being inferred from cell data — ideally with plasma sampled at the same timepoints as the transcriptional readout.
Presentations available
At 290 g/mol, a 5 mg vial amounts to roughly 17 micromoles, a generous quantity for cell work in the micromolar range. Sizes and prices appear on the SLU-PP-332 product page, inside the fat-loss and metabolic collection and the broader research compounds range.
Reconstitution and storage at the bench
One aspect of preparation departs from peptide habits: concentrated stocks belong in DMSO, from which the compound is diluted into assay medium or buffer. Worked through — dissolving 5 mg in 1 mL of DMSO gives 5 mg/mL, which at 290.27 g/mol is roughly 17.2 mM; diluting that 1:1,000 into medium leaves 17.2 micromolar alongside 0.1 percent DMSO, a level most cell assays accept. Planning a stock properly means starting from the tolerable final solvent concentration and working back, not the reverse.
Keep the solid sealed at minus 20 degrees Celsius, protected from light and moisture. Hold solutions at 2 to 8 degrees Celsius for use within the study window; DMSO draws in water, and absorbed moisture alters both effective concentration and freezing behaviour, so sealed single-use portions are standard practice. Our reconstitution guide and the molecular weight and moles note cover more.
Purity, the COA and how to read it
A certificate should carry purity measured by HPLC, a mass spectrometry identity result against the theoretical 290.27 g/mol, the lot number and the analysis date. With a synthetic small molecule from a discovery series, NMR provides the strongest identity evidence available and is worth requesting, since mass cannot separate structural isomers sharing a formula — a live risk for anything built over several synthetic steps. Residual solvent content matters as well, because traces of reaction solvents carried through can influence cell viability at assay concentrations. The peptide certificate's key figure, net peptide content, has no counterpart here. See how to read a COA.
A further difference sets this compound apart from receptor agonists as a laboratory tool. What a nuclear receptor produces is a transcriptional readout, so the natural endpoints are gene expression, protein abundance and functional capacity rather than a signalling event visible within minutes. The fitting assay panel is therefore quantitative PCR or RNA sequencing across the target programme, followed by functional confirmation such as oxygen consumption rate. A group set up for receptor pharmacology but not for transcriptional work will struggle to characterise this compound properly, and that gap in capability is worth checking before ordering material.
Regulatory position
Nowhere is SLU-PP-332 approved, and no clinical development programme exists for it. It is an early-stage research compound whose evidence base is entirely cell culture and rodent work, sold as a laboratory reference chemical. Sports anti-doping authorities also take an interest in compounds of this class.
Related compounds and comparisons
5-Amino-1MQ vs SLU-PP-332 is the most direct comparison. Nearby transcriptional and mitochondrial tools include the PPAR-delta agonist Cardarine (GW-501516) and the mitochondrial uncoupler BAM15.
Questions
Does SLU-PP-332 count as a peptide?
No. This is a synthetic small molecule of 290.27 g/mol containing neither amino acids nor peptide bonds. It appears next to peptides because the metabolic questions overlap, but preparation, storage and analysis follow small-molecule conventions — DMSO stocks and NMR-based identity among them.
What exactly are the estrogen-related receptors?
Orphan nuclear receptors whose name reflects sequence resemblance to the estrogen receptor rather than any ability to bind estrogen. No endogenous ligand is known for them. They act as transcription factors over mitochondrial biogenesis, oxidative phosphorylation and fatty-acid oxidation, partnering the coactivator PGC-1 alpha in skeletal muscle.
Why is it labelled an exercise mimetic?
Because activating the ERRs turns on roughly the same oxidative gene programme that endurance training switches on via PGC-1 alpha. The term records a transcriptional similarity noted in cell and rodent studies; it does not mean the compound is equivalent to exercise, and it makes no claim about outcomes in any organism.
What does pan-agonist mean here, and why care?
It activates ERR alpha, beta and gamma together instead of selecting one isoform. As the three differ in tissue distribution and in part of their target gene sets, no effect seen with this compound can be pinned to one isoform unless the design includes an isoform-selective comparator or a knockdown arm.
Does human data exist?
None at all. Our specification sheet is explicit that the evidence base consists solely of cell culture and rodent studies. There is no clinical trial programme, no published human pharmacokinetics and no human safety information of any kind.
How should stocks be made up?
Dissolve concentrated stocks in DMSO, then dilute into assay medium or buffer. Work backwards from the solvent level the assay will tolerate: 5 mg in 1 mL of DMSO is about 17.2 mM, and diluting 1:1,000 gives 17.2 micromolar with 0.1 percent DMSO remaining.
Why should the certificate include NMR?
A mass result confirms molecular formula but cannot separate structural isomers sharing that formula — a genuine possibility for a compound assembled over several synthetic steps. NMR settles the structure directly. Residual solvent testing counts too, since solvents carried through from the reaction can affect cell viability at assay concentrations.