SLU-PP-332 studies and research data

SLU-PP-332 is the small molecule 4-hydroxy-N'-[(E)-naphthalen-2-ylmethylidene]benzohydrazide (formula C18H14N2O2, 290.3 g/mol), an acyl hydrazone. It is not a peptide. It was reported in 2023 by Billon and colleagues (ACS Chemical Biology 18(4):756-771, PMID 36988910) as a synthetic ERR pan agonist: the authors started from GSK4716, a known agonist scaffold for ERR beta and gamma, and gained about 50-fold ERR alpha potency by structure-based design. The paper says SLU-PP-332 targets all three ERRs with the highest potency for ERR alpha (about 4-fold ERR alpha selectivity over ERR gamma) and that it does not have enough specificity to probe single ERR family members. ChEMBL records half-maximal activation values of 98 nM for ERR alpha, 230 nM for ERR beta and 427 nM for ERR gamma in cell reporter assays (document CHEMBL5620420). The author affiliations in the PMC copy are Washington University School of Medicine (Center for Clinical Pharmacology), Saint Louis University School of Medicine, the University of Florida and other institutes. ERRs are orphan nuclear receptors that control genes for mitochondrial function, fatty acid oxidation and oxidative phosphorylation, and the compound is called an exercise mimetic because in mice it raised oxidative muscle fibres, the expression of an acute aerobic exercise gene program and treadmill endurance. Later mouse papers report effects in obesity and metabolic syndrome (J Pharmacol Exp Ther 2024, PMID 37739806), pressure-overload heart failure (Circulation 2024, PMID 37961903) and the aged kidney (Am J Pathol 2023, PMID 37717940). A 2025 study of human muscle cells from inactive women used it in cell culture only (Front Physiol, PMID 40692696). A 2026 paper from the same group says SLU-PP-332 improves aerobic performance in mice but lacks oral bioavailability, and describes a chemically different, orally active compound, SLU-PP-915 (J Pharmacol Exp Ther, PMID 41421047). Two 2026 drug-testing papers describe 22 in vitro metabolites in human liver fractions for doping control (Drug Test Anal, PMID 41688415) and the analysis of SLU-PP-332 and SLU-PP-915 (Rapid Commun Mass Spectrom, PMID 41588687). No human pharmacokinetic, safety or efficacy study was found. No clinical source gives a human dose, and no approved label exists.

Kind

Small molecule

Formula

C₁₈H₁₄N₂O₂

Identifiers

ChEMBLCHEMBL4208749 (opens in a new tab)PubChem CID5338394 (opens in a new tab)UNII5YW57G7ADL (opens in a new tab)CAS303760-60-3

Development

PreclinicalAcademic origin: the Burris laboratory and collaborators. The 2023 paper lists Washington University School of Medicine (Center for Clinical Pharmacology), Saint Louis University School of Medicine, the University of Florida Genetics Institute, the Salk Institute and other centers. The corresponding author Thomas Burris is described on the Pelagos Pharmaceuticals news page as 'Pelagos founder'. The paper's competing interest statement says T.P.B., B.E. and J.K.W. are stockholders in Myonid Therapeutics, Inc., which focuses on ERR-based therapeutics.Preclinical only. No human study was found: ClinicalTrials.gov 0 studies, ChEMBL max_phase is empty for CHEMBL4208749, and no IND or approval record was found. Pelagos Pharmaceuticals (Houston) lists a 'Pan-ERR Modulator' program with target validation and in vivo proof of concept complete, lead optimization in progress, development candidate nomination in Q4-2027 and IND-enablement in 2028. The page does not name SLU-PP-332 (it speaks of proprietary chemical assets and next-generation molecules), so it is a company program in the same target class and not a trial of this compound. The group's own follow-up compound SLU-PP-915 is described as orally bioavailable; the 2026 abstract says SLU-PP-332 lacks oral bioavailability. Patents: no patent that claims this compound was read. A US patent (11,795,162, Saint Louis University as original assignee, inventors Burris, Walker, Hampton, Haynes, Griffett, Billon and Sitaula) covers thiophene-based ERR gamma inverse agonist compounds, which is a different compound class. The Google Patents page for it does not name SLU-PP-332. The scaffold comes from the earlier GSK4716 series (2023 paper). I did not work out the patent position. Mouse data for reference only (not a human or community dose): the 2023 paper gave 30 mg/kg by intraperitoneal injection for the exposure study and reports no overt toxicity at 50 mg/kg twice daily by intraperitoneal injection for 10 days. These are not human doses. Source (opens in a new tab)

• NAD+ (nicotinamide adenine dinucleotide) evidence
• MOTS-c evidence
• Epitalon evidence
• Glutathione evidence