Lifestyle ⏱ Half-life: Not established in the published literature; human liver microsomal half-life 31.3 minutes in vitro. Preclinical

SLU-PP-332

4-Hydroxy-N'-[(E)-naphthalen-2-ylmethylidene]benzohydrazide (CAS 303760-60-3)

Updated July 24, 2026
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Evidence at a Glance

Regulatory statusPreclinical
Small-molecule pan-ERR agonist (not a peptide); mouse studies only, no human trials.
Human evidenceNone
Animal evidenceLimited

An experimental ERR-agonist 'exercise mimetic' whose endurance and fat-oxidation effects have been demonstrated only in mice, with no human data.

What the research does not support

  • No human trials exist; all endurance and fat-loss data come from rodents.
  • It is not a peptide and is not an approved or clinically validated drug.
  • It does not replace exercise and has no established safety profile in people.
  • Long-term risks of chronic ERR activation, including cardiac or oncologic effects, are unknown.
Half-Life
Not established in the published literature; human liver microsomal half-life 31.3 minutes in vitro.
Mol. Weight
290.32 g/mol (C₁₈H₁₄N₂O₂; monoisotopic 290.1055 Da)
Form
Crystalline small-molecule solid — not a lyophilized peptide.

What is SLU-PP-332?

SLU-PP-332 is a synthetic small molecule, not a peptide. It is an aryl acylhydrazone — 4-hydroxy-N’-[(E)-naphthalen-2-ylmethylidene]benzohydrazide, C18H14N2O2, molecular weight 290.32 g/mol — with no amino acids and therefore no sequence. It is often listed alongside research peptides, which appears to be the source of persistent confusion; the chemistry is unambiguous, documented under CAS 303760-60-3 and PubChem CID 5338394.

It came out of a collaboration between the laboratories of Thomas P. Burris and John K. Walker, by structure-guided modification of the earlier ERR ligand GSK4716; the SLU- prefix refers to Saint Louis University, where the synthetic chemistry was done. It is a pan-agonist of the estrogen-related receptors ERRα, ERRβ and ERRγ, orphan nuclear receptors that regulate mitochondrial biogenesis, oxidative phosphorylation and fatty acid oxidation. Despite the name, the ERRs do not bind estrogen, and SLU-PP-332 is reported inactive at the classical estrogen receptors ERα and ERβ.

Why it is described as an “exercise mimetic”

The label comes from the rodent observation that ERR activation reproduces part of the transcriptional program skeletal muscle mounts after aerobic exercise. Mouse studies report increased oxidative type IIa fibers, greater mitochondrial content and respiratory capacity, higher energy expenditure and fat oxidation, and improved treadmill endurance. The term describes overlap with an exercise-induced gene expression signature in muscle, not equivalence to exercise. A 2026 review in Trends in Endocrinology and Metabolism argues that exercise pills cannot reproduce the multisystem vascular, autonomic, anti-inflammatory and exerkine effects that make physical activity beneficial.

The evidence base is exclusively preclinical: no registered clinical trials, no published human pharmacokinetic, safety or efficacy data, and no regulatory approval anywhere. It is also chemically limited by the standards of its own developers — not orally bioavailable, very low aqueous solubility, a human liver microsomal half-life of roughly half an hour, and no blood-brain barrier penetration. The successor compound SLU-PP-915 was created to obtain an orally active ERR pan-agonist; SLU-PP-332 remains useful as a laboratory chemical probe.

SLU-PP-332 is a research chemical intended for laboratory investigation only and has not been evaluated for human use by any regulatory authority. It is not named in the World Anti-Doping Agency 2026 Prohibited List, contrary to a widely repeated claim that it is banned as a metabolic modulator; as an unapproved investigational substance it nonetheless appears to fall within the S0 non-approved substances class — an application of that definition, not a WADA ruling on this compound.

How SLU-PP-332 Works

SLU-PP-332 is a synthetic pan-agonist of the estrogen-related receptors ERRα, ERRβ and ERRγ — orphan nuclear receptors that do not bind estrogen but drive mitochondrial biogenesis, oxidative phosphorylation and fat oxidation. It is reported inactive at ERα and ERβ. Potency is highest at ERRα (EC50 98/230/430 nM for ERRα/β/γ in the discovery paper), though values vary several-fold with assay format; an independent 2026 group measured 0.22 µM at ERRα. In rodents this reproduces part of the transcriptional program skeletal muscle mounts after aerobic exercise — the basis for the “exercise mimetic” label. Muscle effects appear ERRα-dependent, the cardiac work implicates ERRγ. The biology is not settled: ERRα-null mice are reported lean and resistant to diet-induced obesity, and ERRα inverse agonists have shown antidiabetic activity — a contradiction the authors acknowledge but leave unresolved.

Research Findings

The evidence base is entirely preclinical. There are no registered clinical trials (a ClinicalTrials.gov query returned zero records in July 2026), no published human pharmacokinetic data and no human safety or efficacy data. Primary reports cover exercise capacity in mice (Billon et al., ACS Chem Biol 2023), obesity models (JPET 2024), heart failure (Xu, Circulation 2024) and the aging kidney (Wang, Am J Pathol 2023); a 2025 pilot used human myoblasts in culture, which is not human dosing. Two limitations are stated plainly in the primary literature. SLU-PP-332 is not orally bioavailable — every in vivo study used intraperitoneal injection, and the 2026 paper characterizing its successor compound SLU-PP-915 states so directly. It is also metabolically fragile (human liver microsomal half-life 31.3 minutes, aqueous solubility 0.2 µM), and a 2026 review concluded it is not stable enough to be a conventional drug candidate. No in vivo half-life has been published, and it does not cross the blood-brain barrier. SLU-PP-332 is not named in the WADA 2026 Prohibited List; the widely repeated claim that it is banned as a metabolic modulator is unsupported. As an unapproved investigational substance it would nonetheless fall within the S0 non-approved substances class — a reading of that definition, not a WADA ruling naming this compound.

Dosage & Administration

The following are administration protocols reported in published preclinical studies. They record what investigators did in animal and cell-culture experiments. Every published in vivo study used intraperitoneal injection in rodents.

  • Pharmacokinetics — a single 30 mg/kg intraperitoneal dose in male C57BL/6J mice; two hours later, concentrations were ~0.6 µM in skeletal muscle and ~0.2 µM in plasma (Billon et al., ACS Chem Biol 2023). An earlier preprint reported ~0.8 µM and ~0.1 µM for the same experiment; the published values supersede it.
  • Chronic dosing — 50 mg/kg intraperitoneally twice daily for 10 to 28 days in C57BL/6J mice (Billon et al., ACS Chem Biol 2023; JPET 2024).
  • Acute pre-exercise dosing — a single 50 mg/kg intraperitoneal dose one hour before a treadmill run-to-exhaustion test (Billon et al., 2023).
  • Genetically obese model — 50 mg/kg intraperitoneally twice daily in ob/ob mice; this arm was shortened to 12 days because of reduced tolerance of twice-daily intraperitoneal administration (Billon et al., JPET 2024).
  • Heart failure model — 25 mg/kg intraperitoneally twice daily in pressure-overload heart failure in mice (Xu et al., Circulation 2024).
  • Aging kidney model — eight weeks of treatment in 21-month-old mice; the dose is not stated in the abstract (Wang et al., Am J Pathol 2023).
  • Cell culture — 1–5 µM in C2C12 myoblasts; 10 µM in human cardiomyocyte preparations (Billon et al., 2023; Xu et al., 2024).
  • Route — no published study has administered SLU-PP-332 orally and demonstrated systemic exposure. The successor compound SLU-PP-915 was developed specifically to obtain an orally active ERR pan-agonist.

No standardized human dosing exists for SLU-PP-332. There are no registered clinical trials, no published human pharmacokinetic data and no regulatory approval in any jurisdiction. Every figure above comes from animal or cell-culture research. This compound is for laboratory research use only and is not for human consumption.

Safety & Side Effects

There is no published human safety data for SLU-PP-332 — no clinical trials, no case series, no pharmacovigilance record. Everything below comes from preclinical work in which tolerability was a short, secondary endpoint measured over days to weeks. No chronic toxicology, reproductive toxicology or carcinogenicity study has been published.

Reported in rodent studies

  • Investigators reported no overt toxicity in mice given 50 mg/kg twice daily intraperitoneally for 10 days, with normal complete blood count and electrolytes and no significant change in serum creatine kinase.
  • Over 28 days in chow-fed mice: no change in total body weight, daily food intake, lean mass or locomotor activity.
  • In diet-induced obese mice over 28 days: decreases in plasma total cholesterol, HDL and triglycerides with no change in LDL, and no increase in liver enzymes.
  • A tolerability signal was recorded in the genetically obese (ob/ob) arm, which the authors shortened to 12 days because of reduced tolerance of twice-daily intraperitoneal administration. Whether that reflects the compound, the vehicle, the injection burden or the fragility of that strain is not resolved in the paper.

Chemistry- and target-level concerns raised in the literature

  • Scaffold liability. A 2026 review flags the hydrazide/hydrazone linkage at the core of the molecule as problematic in medicinal chemistry, citing rapid metabolism and possible toxicity, and concludes the compound is not metabolically stable enough to be a conventional drug candidate without further optimization. Nine in vitro metabolites (six Phase-I, three Phase-II) have been characterized; none has been evaluated for its own activity or toxicity.
  • Unresolved oncology question. High ERRα expression is a documented adverse prognostic marker in breast and prostate cancer, and ERRα inverse agonists have been pursued as anticancer agents. The consequences of sustained pharmacological pan-ERR agonism on tumor biology have not been addressed by any published long-term study. This is an open question, not a demonstrated harm — but it is unanswered.
  • Contradictory target biology. ERRα-null mice have been reported lean and resistant to diet-induced obesity, and ERRα inverse agonists have shown antidiabetic activity — findings the study authors acknowledge sit awkwardly beside the benefits attributed to ERR activation.
Important: All safety information is derived from published research, primarily animal studies. No controlled human clinical trial data exists unless explicitly noted. This compound is sold for research purposes only.

Quick Facts

Sequence Not applicable — a synthetic small molecule, not a peptide; it contains no amino acids.
Molecular Weight 290.32 g/mol (C₁₈H₁₄N₂O₂; monoisotopic 290.1055 Da)
Half-Life Not established in the published literature; human liver microsomal half-life 31.3 minutes in vitro.
Form Crystalline small-molecule solid — not a lyophilized peptide.
Available Sizes 5mg
Storage Powder at −20 °C, desiccated and protected from light; DMSO stock solutions at −80 °C (~6 months) or −20 °C (~1 month), aliquoted to avoid freeze–thaw. Practically insoluble in water, so it is not reconstituted in bacteriostatic water the way a peptide would be.

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