SLU-PP-332 (ERR Pan-Agonist)

SLU-PP-332 is a small-molecule research chemical, not a peptide. It is an acylhydrazone formed from 2-naphthaldehyde and 4-hydroxybenzohydrazide, systematically named 4-hydroxy-N’-[(E)-naphthalen-2-ylmethylidene]benzohydrazide. Its formula is C18H14N2O2, its molecular weight 290.3 g/mol, its CAS number 303760-60-3 and its PubChem CID 5338394. A naphthalene ring is joined through a C=N-N-C(=O) linkage to a phenol ring, the imine bond in the E configuration. Nothing in that structure is an amino acid and the compound carries no sequence, which is why the sequence field reads as not applicable.

The literature describes SLU-PP-332 as an agonist of the three estrogen-related receptors, ERRalpha, ERRbeta and ERRgamma. These are orphan nuclear receptors, transcription factors for which no natural hormone ligand is established. Pan-agonist means it acts at all three subtypes rather than selecting one, with the highest reported potency at ERRalpha. The receptors are constitutively active, depend on the PGC-1alpha and PGC-1beta coactivators, and are associated with genes governing mitochondrial biogenesis and oxidative fuel use.

SLU-PP-332 came out of a St Louis medicinal chemistry programme; the prefix SLU denotes Saint Louis University. Shahien and colleagues reported in 2020 that ERRalpha activity could be engineered into GSK4716, an ERRbeta/gamma-selective agonist, producing acylhydrazone pan-agonists (PubMed 32683181).

Billon and colleagues reported SLU-PP-332 in 2023, describing raised cellular respiration in a skeletal muscle cell line and, in mice, a shift toward type IIa oxidative fibres (PubMed 36988910). The same group investigated it in mouse models of metabolic disease (PubMed 37739806). Other laboratories reported cardiac (PubMed 37961903) and aging kidney findings (PubMed 37717940).

The evidence base is entirely preclinical and young. No human trial is published or registered, and most of the in vivo record traces to the originating laboratory. A separate analytical literature characterises its in vitro metabolites for doping control (PubMed 41588687). Every reference here was checked against PubMed retraction and expression-of-concern records; none carries either notice.

The mechanism reported for SLU-PP-332 is transcriptional. It is described as binding the ligand-binding pocket of all three ERR subtypes and stabilising a conformation that favours coactivator engagement, PGC-1alpha most often named, with raised expression of mitochondrial biogenesis and fatty acid oxidation genes (PubMed 36988910).

Two distinctions are useful. Estrogen-related receptors are not estrogen receptors: they share sequence homology with ERalpha but do not bind estradiol, so estrogen receptor pharmacology does not read across. Mechanistic class separates this compound from its neighbours. BAM15 dissipates a proton gradient through membrane biophysics and 5-Amino-1MQ inhibits an enzyme, while SLU-PP-332 acts on gene expression. None of the three is a peptide, unlike SS-31.

A methodology caveat applies. ERRs are constitutively active without a ligand, so agonism is measured as an increase above an already active baseline, usually in cell-based reporter or coactivator-recruitment assays whose readout depends on the coactivator and cell background used. Exposure conditions belong to each study’s methodology.

Sealed SLU-PP-332 is stored at -20°C, shielded from light, in its original container. No duration is asserted here: the window for a batch is documented on its Certificate of Analysis.

Acylhydrazones carry a C=N bond sensitive to hydrolysis and photoisomerisation, so light exclusion and dry storage are the practical points. Capsules are held as printed on the product label rather than frozen.

Reconstitution means returning a solid compound to solution. No preparation procedure appears here: solvent, quantity and technique belong to the methodology of the study being reproduced.

As a general solubility class, SLU-PP-332 is a lipophilic aromatic solid with low aqueous solubility, and DMSO is the co-solvent class usually reported for small molecules of this type in vitro. Solid material is kept dry, since organic solids take up atmospheric moisture and that affects weighed accuracy.

Identity is established by high-performance liquid chromatography with ultraviolet detection and by liquid chromatography with mass spectrometry, the primary check being an observed mass consistent with 290.3 g/mol. Verified purity is documented per lot on the Certificate of Analysis.

Two impurity classes are realistic and neither resolves by mass alone: the synthetic precursors, and the E and Z isomers of the imine. The chromatographic trace on the lot COA is the practical check. Novelle Bio and Catalyst Compounds material is batch tested with a published COA.

Compounds studied alongside SLU-PP-332 in oxidative metabolism work:

• BAM15.
  A small-molecule mitochondrial uncoupler, not a peptide, acting by a non-transcriptional route.
• 5-Amino-1MQ.
  A small-molecule NNMT inhibitor, not a peptide, studied in overlapping rodent models.
• NAD+.
  The cofactor central to the oxidative pathways these receptors regulate, also not a peptide.
• SS-31.
  A mitochondria-targeting tetrapeptide, a research-context comparator, not a structural relative.

Shahien M, Elagawany M, Sitaula S, et al. (2020). Modulation of ERR subtype selectivity. Bioorg Chem.
PubMed 32683181

Billon C, Sitaula S, Banerjee S, et al. (2023). Synthetic ERRalpha/beta/gamma Agonist Induces an ERRalpha-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chem Biol.
PubMed 36988910

Wang XX, Myakala K, Libby AE, et al. (2023). Estrogen-related receptor agonism reverses mitochondrial dysfunction in the aging kidney. Am J Pathol.
PubMed 37717940

Billon C, Schoepke E, Avdagic A, et al. (2024). A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther.
PubMed 37739806

Xu W, Billon C, Li H, et al. (2024). Novel pan-ERR agonists ameliorate heart failure through cardiac fatty acid metabolism. Circulation.
PubMed 37961903

Moller T, Krug O, Thevis M, et al. (2026). In Vitro Metabolism and Analytical Characterization of SLU-PP-332 and SLU-PP-915: Novel Pan-ERR Agonists With Doping Potential. Rapid Commun Mass Spectrom.
PubMed 41588687

Peptides.com lists two SLU-PP-332 research products, both capsules in a solid unit-dose format, from the house brands Novelle Bio and Catalyst Compounds. Both are listed at 1000mcg in 60 count bottles, which are product specifications and not research quantities. Each lot is batch tested with a published Certificate of Analysis, available through Lab Reports.

• Browse all SLU-PP-332 research products
• Novelle Bio SLU-PP-332 Capsules, 1000mcg, 60 count
• Catalyst Compounds SLU-PP-332 Capsules, 1000mcg, 60 count

These products are sold for Research Use Only and are not intended for human consumption.