SLU-PP-332 is not a peptide. It is a synthetic small-molecule pan-ERR (estrogen-related receptor) agonist, a benzohydrazide of about 290 Da, made at Saint Louis University as a chemical tool. The papers call it an exercise mimetic because it turns on an aerobic-exercise gene program in mouse muscle. PeptidePrices still tracks vendor listings because those vials sit next to research peptides.
The published record is almost entirely preclinical: cells and mice. No completed human efficacy trial was identified. Mouse treadmill time, fat-mass NMR, and albuminuria are not a human result. Research-vendor vials are not the laboratory compound.
The site already has a short research profile. This explainer is the evidence map that page does not carry. This is the 10:07 Research Roundup, not an Industry News incretin story.
What SLU-PP-332 is
Billon, Sitaula, Banerjee, Burris, and colleagues (ACS Chemical Biology, 21 April 2023, PMID 36988910, DOI 10.1021/acschembio.2c00720, PMC11584170) named the tool SLU-PP-332. Methods give (E)-4-hydroxy-N'-(naphthalen-2-ylmethylene)benzohydrazide, C18H14N2O2, HRMS [M+H]+ 291.11280. PubChem CID 5338394 lists the same formula, about 290.3 Da, and CAS 303760-60-3. Some vendor certificates print CID 135741221. That CID is a different molecule (C20H19NO3).
The scaffold started from GSK4716, an older ERRβ/γ agonist. A naphthalene in place of the isopropyl-phenyl group raised ERRα potency. In a full-length ERR reporter assay, EC50 values were about 98 nM (ERRα), 230 nM (ERRβ), and 430 nM (ERRγ): 4.4-fold ERRα over ERRγ and 2.3-fold over ERRβ. It did not move ERα, ERβ, or the other nuclear receptors they screened. Limited proteolysis supported ERRα binding. Differential scanning fluorimetry supported ERRγ binding. Those are dish numbers, not a human potency claim.
SLU-PP-332 is not NAD+, not SS-31, and not a peptide. Sharing a mitochondria or exercise conversation is not sharing a molecule.
| Thing | What it is | What a paper can show |
|---|---|---|
| ERRα / β / γ | Orphan nuclear receptors for oxidative-metabolism genes | Mouse KO or overexpression phenotypes |
| SLU-PP-332 | Synthetic pan-ERR agonist, highest potency at ERRα | Culture EC50s, mouse PK, mouse endurance and metabolism |
| Exercise mimetic (paper use) | A tool that induces an aerobic-exercise gene set | Overlap with published acute-exercise DEG lists |
| Exercise mimetic (marketing use) | A claim that a vial replaces training in people | Nothing in this source set |
| Research-vendor vial | A catalog chemical sold as SLU-PP-332 | Paperwork, not a trial product |
A COA check can test whether a certificate names a real lab. It cannot turn a catalog vial into the Burris-lab reagent. SLU-PP-332 is not approved for human use.
What ERRs are, and what "exercise mimetic" means
ERRs (ERRα/NR3B1, ERRβ/NR3B2, ERRγ/NR3B3) were the first orphan nuclear receptors identified. They are homologous to estrogen receptors, but they do not bind classic estrogens. They are constitutively active. Target genes include fatty-acid oxidation, TCA-cycle, mitochondrial-biogenesis, and oxidative-phosphorylation enzymes. Expression is high in energy-demand tissues, including skeletal muscle.
The ACS rationale is genetic, not clinical. Muscle-specific ERRα deletion reduced mitochondrial biogenesis and repair. Whole-body ERRα-null mice had less muscle and less endurance. Muscle ERRγ overexpression raised oxidative fibers and endurance without training. ERRβ is low in skeletal muscle. That package is why the authors wanted an ERRα-competent agonist that could be used in live mice.
"Exercise mimetic" here is a gene-program claim. After chronic dosing, RNA-seq from quadriceps and gastrocnemius overlapped published acute-aerobic-exercise DEG lists from mice and from lean humans after one cycling bout. The human set is a comparison transcriptome, not a treated-human arm. Shared genes included Ddit4 and Slc25a25. The paper treats Ddit4 as an ERRα target: induction was lost in ERRα-null primary myocytes and retained in ERRγ-null myocytes. That is a mouse-and-dish mechanism. It is not proof that a research chemical replaces training.
The authors also limit the tool. At the doses they used, all three ERRs would be on. Transient pharmacology is not chronic ERR overexpression.
What the studies actually tested
Three primary mouse papers define the public map. A 2026 SAR paper is chemistry support, not efficacy.
Billon et al., ACS Chemical Biology, 2023. Discovery and exercise-capacity paper. In C2C12 myocytes, Pdk4 rose, maximum mitochondrial respiration rose after 24 hours, and MitoTracker staining increased. Mice received 30 mg/kg intraperitoneal for PK and 50 mg/kg twice daily intraperitoneal for most in-vivo arms. After 15 days at thermoneutrality (30 °C), quadriceps showed more SDH staining, smaller fibers, more mitochondria by electron microscopy and mtDNA, and more type IIa fibers. After about one week at 50 mg/kg twice daily, sedentary mice ran about 70% longer and about 45% further to exhaustion than vehicle mice. A two-week arm reported higher grip strength. RNA-seq after 10 days found 442 DEGs in quadriceps and 238 in gastrocnemius (FDR < 0.05, |FC| > 1.5). Ddit4 was the top shared up-gene. A single 50 mg/kg dose raised gastrocnemius Ddit4 about 3-fold at 1 hour in sedentary mice; a 40-minute run raised it about 6-fold; both together about 11-fold. Slc25a25 rose about 11-fold at 1 hour after drug or exercise and was gone by 3 hours. Muscle-specific ERRα knockout mice did not gain the endurance phenotype. Results text for that arm is 50 mg/kg twice daily for 14 days; methods list 25 mg/kg for 15 days.
Billon et al., Journal of Pharmacology and Experimental Therapeutics, 2024 (PMID 37739806, DOI 10.1124/jpet.123.001733, PMC10801787). Same Burris/SLU lineage, different question: metabolic syndrome in mice. Dose: 50 mg/kg intraperitoneal twice daily. Chow-fed wild-type mice, 28 days, n = 8/arm, thermoneutrality: no total-body-weight difference, less fat-mass gain, no food-intake, lean-mass, or activity change. RER fell within 2 hours of the first dose. Fatty-acid oxidation by Frayn's equation was 25% higher than vehicle. Energy expenditure rose. Chow-fed glucose and pyruvate tolerance tests did not improve. DIO mice (8 weeks of 60% fat diet, then 28 days of drug on the same diet, n = 7/arm) showed progressive weight loss. After 28 days the drug group weighed about 12% less. Vehicle gained about 5 g of fat mass; drug gained less than 0.5 g. Fasting glucose and insulin were lower. Glucose tolerance improved. An insulin-tolerance test did not. Liver triglycerides, steatosis, and white-adipocyte size fell. CLAMS again showed lower RER and higher fatty-acid oxidation and resting energy expenditure. ob/ob methods shortened the arm to 12 days because twice-daily intraperitoneal dosing was poorly tolerated; the Figure 4 caption says 15 days. Adiposity and liver weight fell. Food intake did not. RER, fatty-acid oxidation, energy expenditure, and hepatic steatosis moved in the same direction as the other obese arms. JPET restates the ACS PK pair as 0.2 μM plasma and 0.6 μM muscle at 6 hours after 30 mg/kg. The ACS results figure is the 2-hour pair. Use the ACS primary for the clock time.
Wang et al., American Journal of Pathology, 2023 (PMID 37717940, DOI 10.1016/j.ajpath.2023.07.008, PMC10734281). Georgetown/NIA aging-kidney study. Corresponding authors are Xiaoxin X. Wang and Moshe Levi. Burris, Billon, Elgendy, Walker, and Chatterjee are listed as co-authors (compound source). Different senior authors and a different organ. Not a fully independent SLU replication. Twenty-one-month NIA-colony male C57BL/6 mice received 25 mg/kg/day intraperitoneal for 8 weeks versus 3% DMSO vehicle. The paper reports lower age-related albuminuria and kidney weight, higher podocin, lower injury transcripts, restored mitochondrial ultrastructure, and lower cGAS-STING and STAT3 marks. ERRs were also lower in aging human kidney tissue. That human material is observational expression, not patient dosing.
Okda et al., International Journal of Biological Macromolecules, April 2026 (PMID 41850449, DOI 10.1016/j.ijbiomac.2026.151450, PMC13112601). SAR on the scaffold: potency, solubility, metabolic stability. Burris and Elgendy are on this paper too. Chemistry support, not efficacy.
A registered interventional human efficacy trial of SLU-PP-332 was not identified in the evidence review for this article.
| Paper | Design | Human SLU-PP-332 exposure |
|---|---|---|
| Billon 2023, ACS Chem Biol | C2C12 plus mouse PK, histology, treadmill, RNA-seq, muscle ERRα KO | None |
| Billon 2024, J Pharmacol Exp Ther | Chow, DIO, and ob/ob mouse metabolism | None |
| Wang 2023, Am J Pathol | 21-month mouse kidney; aging human kidney expression | None as a drug. Human arm is tissue ERR levels. |
| Okda 2026, Int J Biol Macromol | SAR / analogs | None |
Research doses reported in animals and culture
SLU-PP-332 is not approved for human use. The table reports what laboratories used. It is not a dosage guide and it is not a consumer protocol.
| Setting | Reported exposure | Source |
|---|---|---|
| ERR reporter assay | EC50 about 98 / 230 / 430 nM (ERRα / β / γ) | Billon et al., 2023 |
| C2C12 methods | 10 μM | Billon et al., 2023 |
| Mouse PK | 30 mg/kg i.p.; plasma ~0.2 μM, muscle ~0.6 μM at 2 h | Billon et al., 2023 |
| Mouse safety window | 50 mg/kg b.i.d. i.p., 10 days; no overt toxicity on the reported CBC/electrolytes; CK unchanged | Billon et al., 2023 |
| Mouse histology | 50 mg/kg b.i.d. i.p., 15 days, thermoneutrality | Billon et al., 2023 |
| Mouse treadmill | Results: 50 mg/kg b.i.d. i.p., 7 days. Methods: 6 days | Billon et al., 2023 |
| Muscle ERRα KO run | Results: 50 mg/kg b.i.d. i.p., 14 days. Methods: 25 mg/kg, 15 days | Billon et al., 2023 |
| Chow and DIO metabolism | 50 mg/kg i.p. twice daily, 28 days | Billon et al., 2024 |
| ob/ob metabolism | 50 mg/kg i.p. twice daily, 12 days (methods); 15 days in the figure caption | Billon et al., 2024 |
| Aging-kidney mice | 25 mg/kg/day i.p., 8 weeks | Wang et al., 2023 |
That does not make 50 mg/kg an approved dose. It also does not make 25 mg/kg/day, 30 mg/kg, 10 μM, or 98 nM an approved dose. Mouse intraperitoneal milligrams-per-kilogram are not a human milligram conversion. No anecdotal human-equivalent translation appears here. The ACS wild-type treadmill vehicle was 10% Tween, 10% DMSO, 80% PBS. That is a study vehicle, not a reconstitution protocol.
What this does not mean
- It is not human efficacy. No identified trial gave SLU-PP-332 to people and measured a clinical endpoint.
- It is not an approved exercise, obesity, diabetes, or kidney drug. FDA has not approved SLU-PP-332 for any indication.
- It is not a peptide. Catalog placement does not change the chemistry.
- Mouse treadmill time is not a human PED result. About 70% longer and 45% further is one sedentary C57BL/6J protocol. Muscle ERRα deletion removed the gain.
- A 12% lower DIO body weight is not a human weight-loss trial. That figure is 28 days, 50 mg/kg twice daily, n = 7. Chow-fed mice did not lose total body weight.
- A 25% fatty-acid-oxidation rise is one chow CLAMS calculation. It is not human calorimetry.
- Improved DIO glucose tolerance is not an insulin-sensitizer label. The DIO insulin-tolerance test did not move.
- Wang's albuminuria change is not a human kidney therapy. Human data there are aging-kidney ERR expression.
- Gene-set overlap with a human cycling transcriptome is not a treated-human study.
- A research-vendor listing is not the study product. Some certificates print the wrong PubChem CID.
- This is not medical advice, and it is not a consumer dosing protocol.
- This is not an incretin story. SLU-PP-332 is not GLP-1, GIP, or the morning Industry News slot.
Related maps stay on their own molecules: Humanin, FOXO4-DRI, and NAD+ IV.
Limitations
The human gap is first. Nobody in these papers received SLU-PP-332 as a drug. Wang's human kidney work is expression, not treatment.
Two of the three in-vivo efficacy papers share the Burris/SLU senior-author line. Wang/Levi change the organ and the corresponding authors, but the compound chemists remain on the author list.
Sample sizes are small: six mice on the ACS treadmill methods line, seven in DIO, eight in chow CLAMS, often 5 to 6 in Wang kidney assays.
Dose lines conflict inside papers. ACS results and methods disagree on knockout milligrams and on 6 versus 7 treadmill days. JPET methods say 12 days for ob/ob; the figure caption says 15.
Safety is a short mouse window. Ten days of 50 mg/kg twice daily with a CBC/electrolyte table is not chronic toxicology. JPET reported only minor cholesterol and liver-enzyme shifts in chow mice and no liver-enzyme rise in DIO.
Thermoneutrality (30 °C) was used to avoid ERR effects on facultative thermogenesis. Housing temperature is part of the phenotype. The ACS discussion names sarcopenia, muscular dystrophy, and metabolic disease as possible uses. That is speculation after mouse data.
Commercial SLU-PP-332 is a separate problem. Catalog strength, salt, and identity are not established by a mouse paper.
What to watch
- A first registered interventional human protocol. Until one exists, SLU-PP-332 stays preclinical.
- Peer-reviewed human pharmacokinetics after a defined lot. Mouse 0.2 μM / 0.6 μM is not human PK.
- Independent in-vivo replication that does not share the SLU author list. Endurance and DIO still sit in one lab line.
- Whether later papers keep 50 mg/kg twice daily or the 25 mg/kg/day kidney schedule.
- Paralog-selective agonists. Okda 2026 is SAR, not efficacy.
- How vendors describe the molecule. ACS 2023 language is not a sterility claim. Check the CID on the certificate.
FAQs
Is SLU-PP-332 a peptide?
No. It is a synthetic benzohydrazide (about 290 Da). PeptidePrices lists it because vendors sell it next to peptides.
Has it been tested in humans?
No interventional efficacy trial was identified. Wang 2023 has aging-kidney ERR expression, not patient dosing.
Did it replace exercise or treat obesity in people?
No. Billon 2023 and 2024 treated mice. Those are rodent phenotypes.
What dose was used?
Papers reported 50 mg/kg intraperitoneal twice daily in most Burris-lab mouse arms, 30 mg/kg for PK, 25 mg/kg/day for 8 weeks in Wang's aged mice, and nanomolar-to-10 μM concentrations in culture. SLU-PP-332 is not approved for human use. That does not make 50 mg/kg an approved dose.
Is a research-vendor vial the ACS 2023 compound?
No. Catalog listings are a different market. Some certificates print CID 135741221, which is not this molecule.
Is this a NAD+, SS-31, FOXO4-DRI, Humanin, or GLP-1 story?
No. Those molecules have separate maps. This is not an incretin or Industry News article.
This article is for general informational purposes only and is not medical advice. Talk to a licensed clinician about personal medical decisions. SLU-PP-332 is an investigational small-molecule ERR agonist studied in cells and mice. Nothing here is a dosing protocol or a recommendation to obtain an unapproved product.
Continue your research
- SLU-PP-332 listings
- SLU-PP-332 research profile
- NAD+ IV
- FOXO4-DRI
- Humanin
- SS-31 (elamipretide)
- COA Authenticity Checker
Sources
- Billon C, Sitaula S, Banerjee S, et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(4):756-771. PMID 36988910. DOI 10.1021/acschembio.2c00720
- Billon C, Schoepke E, Avdagic A, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024;388(2):232-240. PMID 37739806. DOI 10.1124/jpet.123.001733
- Wang XX, Myakala K, Libby AE, et al. Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney. Am J Pathol. 2023;193(12):1969-1987. PMID 37717940. DOI 10.1016/j.ajpath.2023.07.008
- Okda HE, Zhao P, Hayes M, et al. Chemical optimization of the exercise mimetic SLU-PP-332 enables insight into estrogen-related receptor signaling. Int J Biol Macromol. 2026;355:151450. PMID 41850449. DOI 10.1016/j.ijbiomac.2026.151450
- PubChem CID 5338394. SLU-PP-332 / 4-hydroxy-N-[(E)-naphthalen-2-ylmethylideneamino]benzamide. CAS 303760-60-3