Beta notice: PeptiJournal is currently in beta. Calculator math and RUO research protocol summaries should be independently double-checked against source literature before use in any research workflow.

    §Weight LossResearch protocol

    SLU-PP-332.

    PRECLINICAL RESEARCH COMPOUND: SLU-PP-332 is a synthetic pan-agonist of estrogen-related receptors (ERRα/β/γ) studied exclusively in murine models for its ability to activate an aerobic-exercise ge...

    Last updated:

    Research Use Only. PeptiJournal supports private research documentation and calculation support. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.

    Calculated-volume support unavailable

    This selected cited guide does not contain one unambiguous vial, per-event amount, cadence, and diluent set. No value was inferred from general library metadata. Review the cited table below before creating a private Research Use Only record.

    Cited protocol & reconstitution guide

    Source-backed reference fields by phase, including any volume fields authored in the cited guide.

    Daily — community subcutaneous range

    250 mcg to 1.5 mg per day

    Units / volume15–90 units (0.15–0.90 mL)

    Overview

    Overview

    PRECLINICAL RESEARCH COMPOUND: SLU-PP-332 is a synthetic pan-agonist of estrogen-related receptors (ERRα/β/γ) studied exclusively in murine models for its ability to activate an aerobic-exercise gene program, enhance mitochondrial function, and improve endurance and cardiometabolic phenotypes[1][2][3]. No human trials have been conducted as of November 2025. This educational protocol reflects published murine regimens using intraperitoneal administration. Evidence Base: Preclinical only—in vivo

    Category
    Weight Loss

    Mechanism

    SLU-PP-332

    Mechanism of action

    Mechanism of action

    Short version: SLU-PP-332 binds to ERRα, and to a lesser extent ERRβ and ERRγ. These are transcription factors in the cell nucleus that control how many mitochondria a cell builds, how efficiently those mitochondria burn fat, and how much oxidative capacity the cell has. When you run, muscle cells upregulate these same receptors. SLU-PP-332 does it pharmacologically. Think of ERRα as the master volume knob for a cell's aerobic machinery — SLU-PP-332 turns that knob up. ERRα is highly expressed in energy-demanding tissues such as skeletal muscle, heart, brown adipose tissue, and liver. When activated, it switches on genes for mitochondrial biogenesis, oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation. In the Billon 2023 paper, a single 25 mg/kg intraperitoneal dose in mice was enough to induce an acute aerobic exercise transcriptional signature in muscle within hours. Cell assays show SLU-PP-332 activates all three ERR isoforms but is roughly four-fold more potent at ERRα than ERRγ , with ERRβ in between (ERRα EC50 ≈ 98 nM, ERRγ EC50 ≈ 430 nM). ERRα works in partnership with PGC-1α, the master coactivator of mitochondrial biogenesis. Together they drive expression of nuclear-encoded mitochondrial genes, increasing both the number and efficiency of mitochondria in muscle and cardiac tissue. In the Billon 2023 study, 50 mg/kg twice daily for 28 days increased succinate dehydrogenase-positive oxidative muscle fibers and raised OXPHOS complex protein levels. In diet-induced obese mice and ob/ob mice, 50 mg/kg twice daily for 28 days increased whole-body energy expenditure and fatty acid oxidation, reduced fat mass, lowered cholesterol and triglycerides, and improved insulin sensitivity without changing food intake . That is a metabolic-rate mechanism, not an appetite-suppression mechanism like Semaglutide or Tirzepatide . In a pressure-overload heart-failure mouse model, six weeks of SLU-PP-332 improved ejection fraction, reduced fibrosis, and increased survival. The authors attributed the effect mainly to ERRγ engagement in cardiomyocytes, which normalized fatty acid metabolism and mitochondrial function without reversing hypertrophy itself. The practical takeaway is that ERRα appears to drive most skeletal-muscle effects, while ERRγ carries more of the cardiac signal. Put together, SLU-PP-332 reproduces many of the cellular adaptations of endurance training at the transcriptional level. What it does not reproduce is the mechanical loading of actual exercise, so tendon, bone, and connective-tissue adaptations are not part of the promise. It is a metabolic research tool, not a substitute for training.

    Key research findings
    • 01

      SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors (ERRα/β/γ) with the highest reported potency at ERRα. In a skeletal-muscle cell line it increased mitochondrial function and cellular respiration and triggered an ERRα-dependent gene program overlapping with the acute aerobic-exercise response, which is why it is described in the literature as an 'exercise mimetic' / ERR chemical probe (in vitro / cell-based; ACS Chem Biol 2023, PMID 36988910, doi:10.1021/acschembio.2c00720).

    • 02

      In mice, SLU-PP-332 increased type IIa oxidative skeletal-muscle fibers and enhanced running endurance, with ERRα activation reported as critical for the endurance effect (animal model; ACS Chem Biol 2023, PMID 36988910).

    • 03

      In diet-induced obese and ob/ob mice, SLU-PP-332 administration was associated with increased energy expenditure and fatty-acid oxidation, decreased fat-mass accumulation, and improved insulin sensitivity; the researchers attributed the reduction in fat mass to increased energy expenditure rather than to appetite/food-intake suppression (animal model; J Pharmacol Exp Ther 2023, PMID 37739806, doi:10.1124/jpet.123.001733).

    • 04

      Two structurally distinct pan-ERR agonists (SLU-PP-332 and the related SLU-PP-915) improved ejection fraction, reduced fibrosis, and increased survival in a mouse pressure-overload heart-failure model, with multi-omics work identifying ERRγ as the main mediator of the metabolic/transcriptional response (animal model + in vitro; Circulation 2023, PMID 37961903, doi:10.1161/CIRCULATIONAHA.123.066542).

    • 05

      In a pilot study, primary myoblasts isolated from skeletal muscle of physically inactive women and treated with SLU-PP-332 showed upregulation of PGC-1α, ERRα, SIRT1, and FNDC5, reduced markers of oxidative stress/senescence, and increased myotube formation. This is human-derived cell culture work, not in vivo human dosing (ex vivo / human primary cells; Front Physiol 2025, PMID 40692696, doi:10.3389/fphys.2025.1616693).

    • 06

      A 2026 systematic review of 2020–2024 preclinical literature concluded pan-ERR agonism (SLU-PP-332 / SLU-PP-915) is a promising exercise-mimetic strategy in animal and cell models but explicitly stated that clinical trials are still needed to confirm efficacy and safety in humans. Separately, SLU-PP-332 has been reported to lack oral bioavailability (dosed by injection in rodent studies), which motivated the orally bioavailable analogue SLU-PP-915 (systematic review + animal model; Rev Med Chil 2026, PMID 42024694, doi:10.4067/s0034-98872026000200237; J Pharmacol Exp Ther 2025, PMID 41421047).

    Primary source: Billon 2023 (ACS Chemical Biology): Preclinical in vivo, 15-28 days, C57BL/6J mice (n = 8-10 per group). 25 mg/kg IP for 15 days increased treadmill endurance; 50 mg/kg twice daily for 28 days raised oxidative muscle fibers and OXPHOS proteins. Billon 2024 (Journal of Pharmacology and Experimental Therapeutics): Preclinical in vivo, 12-28 days, DIO C57BL/6J and ob/ob mice (n = 7-8 per group). 50 mg/kg twice daily reduced fat mass, lowered cholesterol and triglycerides, reduced adipocyte size, and improved glucose tolerance. Xu 2024 (Circulation): Preclinical in vivo, 6 weeks, C57BL/6J mice, pressure-overload TAC heart-failure model. Improved ejection fraction, reduced fibrosis, and increased survival; effects mediated mainly via ERRγ in cardiomyocytes. Wang 2023 (American Journal of Pathology): Preclinical in vivo, 8 weeks, aged mice, aging-kidney model. 25 mg/kg/day reduced albuminuria, preserved podocin, reversed mitochondrial dysfunction and inflammation. Human-trial gap: No registered or completed human clinical trial as of June 2026 per ClinicalTrials.gov. All efficacy claims circulating for SLU-PP-332 in humans rely on mouse-to-human extrapolation.

    Protocol Reference

    Protocol reference

    Research Use Only. PeptiJournal supports private research documentation and calculation support. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.

    Commonly cited research range: 1.25–2.5 mg, daily.

    Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.

    Cited protocol & reconstitution guide

    Source-backed reference fields by phase, including any volume fields authored in the cited guide.

    Daily — community subcutaneous range

    250 mcg to 1.5 mg per day

    Units / volume15–90 units (0.15–0.90 mL)

    Titration protocol

    1. Ongoing — once dailyStart
      250 mcg to 1.5 mg per day

      Drawn from a reconstituted 5 mg vial at 2,500 mcg/mL; 250 mcg = 10 units, 500 mcg = 20 units, 1 mg = 40 units, 1.5 mg = 60 units on a U-100 syringe. Source reference cycle lengths: 4 weeks (review at Week 4), 6-8 weeks (review at Week 6), or 12 weeks (review at Week 8 and Week 12).

    Storage & Handling

    Storage requirements(typical for most peptides)

    ❄️
    Lyophilized (powder)
    -20°C (frozen)

    Can be stored for extended periods. Protect from moisture.

    🧊
    Reconstituted
    2-8°C (refrigerated)

    Store in refrigerator door. Never freeze after reconstitution.

    ⏱️
    Stability window
    28-30 days after reconstitution

    Label vials with reconstitution date. Discard if cloudy.

    Reconstitution steps

    1. 01🌡️01 Warm the vial — Let the lyophilized vial reach room temperature for 5-10 minutes.
    2. 02🧴02 Wipe the stoppers — Use an alcohol swab on both the SLU-PP-332 vial and the bacteriostatic water vial.
    3. 03💉Draw 3 mL bacteriostatic water into a sterile syringe — this 5 mg vial yields 1.67 mg/mL.
    4. 04💧04 Inject slowly — Inject the water down the inside wall of the vial — do not blast diluent directly onto the powder.
    5. 05🔄05 Swirl to dissolve — Swirl gently until fully dissolved. Do not shake vigorously.
    6. 06🏷️06 Label the vial — Note the reconstitution date and the final concentration (2,500 mcg/mL) on the vial label.
    7. 07❄️07 Refrigerate and protect from light — Store at 2-8°C (35.6-46.4°F) protected from light.
    8. 08💉Critical: This guide reflects preclinical murine research only. This information is for educational and research purposes exclusively—not for human consumption. No human safety or efficacy data exist for SLU-PP-332.

    Additional storage notes

    Lyophilized powder (vial)

    -4°F (-20°C) long-term, or 35.6-46.4°F (2-8°C)

    Reconstituted solution (vial)

    35.6-46.4°F (2-8°C), protect from light

    Oral tablets (sealed bottle)

    Cool, dry room temperature, away from light and humidity

    DMSO stock solution (lab)

    -112°F (-80°C) ideal; -4°F (-20°C) acceptable

    Clinical Evidence

    Clinical evidence

    Studied exclusively in murine models as an exercise-mimetic research compound; no human data exist.

    Billon 2023 (ACS Chemical Biology): Preclinical in vivo, 15-28 days, C57BL/6J mice (n = 8-10 per group). 25 mg/kg IP for 15 days increased treadmill endurance; 50 mg/kg twice daily for 28 days raised oxidative muscle fibers and OXPHOS proteins. Billon 2024 (Journal of Pharmacology and Experimental Therapeutics): Preclinical in vivo, 12-28 days, DIO C57BL/6J and ob/ob mice (n = 7-8 per group). 50 mg/kg twice daily reduced fat mass, lowered cholesterol and triglycerides, reduced adipocyte size, and improved glucose tolerance. Xu 2024 (Circulation): Preclinical in vivo, 6 weeks, C57BL/6J mice, pressure-overload TAC heart-failure model. Improved ejection fraction, reduced fibrosis, and increased survival; effects mediated mainly via ERRγ in cardiomyocytes. Wang 2023 (American Journal of Pathology): Preclinical in vivo, 8 weeks, aged mice, aging-kidney model. 25 mg/kg/day reduced albuminuria, preserved podocin, reversed mitochondrial dysfunction and inflammation. Human-trial gap: No registered or completed human clinical trial as of June 2026 per ClinicalTrials.gov. All efficacy claims circulating for SLU-PP-332 in humans rely on mouse-to-human extrapolation.

    1. 01SLU-PP-332 is a synthetic small-molecule pan-agonist of the estrogen-related receptors (ERRα/β/γ) with the highest reported potency at ERRα. In a skeletal-muscle cell line it increased mitochondrial function and cellular respiration and triggered an ERRα-dependent gene program overlapping with the acute aerobic-exercise response, which is why it is described in the literature as an 'exercise mimetic' / ERR chemical probe (in vitro / cell-based; ACS Chem Biol 2023, PMID 36988910, doi:10.1021/acschembio.2c00720).
    2. 02In mice, SLU-PP-332 increased type IIa oxidative skeletal-muscle fibers and enhanced running endurance, with ERRα activation reported as critical for the endurance effect (animal model; ACS Chem Biol 2023, PMID 36988910).
    3. 03In diet-induced obese and ob/ob mice, SLU-PP-332 administration was associated with increased energy expenditure and fatty-acid oxidation, decreased fat-mass accumulation, and improved insulin sensitivity; the researchers attributed the reduction in fat mass to increased energy expenditure rather than to appetite/food-intake suppression (animal model; J Pharmacol Exp Ther 2023, PMID 37739806, doi:10.1124/jpet.123.001733).
    4. 04Two structurally distinct pan-ERR agonists (SLU-PP-332 and the related SLU-PP-915) improved ejection fraction, reduced fibrosis, and increased survival in a mouse pressure-overload heart-failure model, with multi-omics work identifying ERRγ as the main mediator of the metabolic/transcriptional response (animal model + in vitro; Circulation 2023, PMID 37961903, doi:10.1161/CIRCULATIONAHA.123.066542).
    5. 05In a pilot study, primary myoblasts isolated from skeletal muscle of physically inactive women and treated with SLU-PP-332 showed upregulation of PGC-1α, ERRα, SIRT1, and FNDC5, reduced markers of oxidative stress/senescence, and increased myotube formation. This is human-derived cell culture work, not in vivo human dosing (ex vivo / human primary cells; Front Physiol 2025, PMID 40692696, doi:10.3389/fphys.2025.1616693).
    6. 06A 2026 systematic review of 2020–2024 preclinical literature concluded pan-ERR agonism (SLU-PP-332 / SLU-PP-915) is a promising exercise-mimetic strategy in animal and cell models but explicitly stated that clinical trials are still needed to confirm efficacy and safety in humans. Separately, SLU-PP-332 has been reported to lack oral bioavailability (dosed by injection in rodent studies), which motivated the orally bioavailable analogue SLU-PP-915 (systematic review + animal model; Rev Med Chil 2026, PMID 42024694, doi:10.4067/s0034-98872026000200237; J Pharmacol Exp Ther 2025, PMID 41421047).

    Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.

    References

    Literature references

    Published research articles and sources related to SLU-PP-332.

    1. 01
      Billon C, Sitaula S, Banerjee S, Welch R, Elgendy B, Hegazy L, et al. Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chemical Biology (2023)
      et al. (2023)
    2. 02
      Billon C, Schoepke E, Avdagic A, Chatterjee A, Butler A, Elgendy B, et al. A Synthetic ERR Agonist Alleviates Metabolic Syndrome. Journal of Pharmacology and Experimental Therapeutics (2024)
      et al. (2024)
    3. 03
      Xu W, Billon C, Li H, Wilderman A, Qi L, Graves A, et al. Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation (2024)
      et al. (2024)
    4. 04
      Wang XX, Myakala K, Libby AB, Krawczyk E, Panov J, Jones BA, et al. Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney. American Journal of Pathology (2023)
      et al. (2023)
    5. 05
      MedChemExpress SLU-PP-332 | ERR Agonist product data sheet. MedChemExpress (2024)
      et al. (2024)
    6. 06
      Cayman Chemical SLU-PP-332 product data sheet (CAS 303760-60-3). Cayman Chemical (2024)
      et al. (2024)
    7. 07
      Shahien M, Elgendy B, Hegazy L, Patouret R, Walker JK, Burris TP. Development of synthetic agonists of estrogen-related receptors (ERRs) based on an aniline-based pan-agonist scaffold. Journal of Medicinal Chemistry (precursor scaffold context) (2023)
      et al. (2023)
    8. 08
      Frontiers in Physiology editorial team Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study. Frontiers in Physiology (2025)
      et al. (2025)
    9. 09
      Nasri H. New hopes on 'SLU-PP-332' as an effective agent for weight loss with indirect kidney protection efficacy; a nephrology point of view. Journal of Renal Endocrinology (2024)
      et al. (2024)
    10. 10
      PubChem PubChem entry for SLU-PP-332 (CAS 303760-60-3). PubChem / NCBI (2024)
      et al. (2024)
    11. 11
      ClinicalTrials.gov Registry search for 'SLU-PP-332' confirming no registered or completed human trials. ClinicalTrials.gov (2026)
      et al. (2026)
    12. 12
      World Anti-Doping Agency WADA Prohibited List — class S4.5 metabolic modulators (ERR agonists as a class). WADA (2026)
      et al. (2026)
    Search PubMed for SLU-PP-332

    Observed Effects

    Observed effects in cited research

    Mouse-study observations
    • In the Billon 2023 and Billon 2024 studies, mice dosed at 25-50 mg/kg IP for up to 28 days showed no overt toxicity, no sickness-related weight loss, no liver-enzyme signal at the doses tested, and no cardiac dysfunction. In the Xu 2024 heart-failure study the compound improved cardiac function rather than worsening it; in the Wang 2023 kidney study it was renoprotective rather than nephrotoxic.
    Broad tissue exposure
    • ERR receptors are widely expressed across heart, brain, kidney, liver, adipose tissue, and gut, so systemic pan-ERR agonism is not tissue-selective.
    Appetite changes
    • Some community users report appetite changes, though food intake was not significantly altered in the DIO mouse studies.
    Sleep disturbance and stimulation
    • Informal reports describe a more stimulatory feeling and sleep disruption; no controlled data exist.
    Resting heart rate
    • A subset of community users report increased resting heart rate. There is no controlled human data confirming or quantifying this effect.
    Cardiovascular unknowns
    • Chronic high-dose human data do not exist, even though preclinical agonist data looks cardioprotective in heart-failure models.
    Oncology unknowns
    • ERRα participates in some cancer-metabolism pathways, leaving long-term cancer-risk questions open.
    Drug interactions
    • Hepatic metabolism and CYP-pathway interactions in humans are uncharacterized.
    Serious adverse events
    • No serious adverse events have been reported in any published rodent study of SLU-PP-332 at the doses and durations tested. No long-term toxicology study beyond 12 weeks has been published in any species. Washout in mice appears relatively fast given the short exposure window, but that is an animal-PK inference, not a human fact.

    Research Considerations

    Research considerations

    Research Use Only - not for human or veterinary therapeutic use. Evidence is strictly preclinical (cell and/or animal models); it is a research compound, not a therapy, and has not been evaluated for human safety. Consult a licensed healthcare professional for any clinical decisions.

    • Pregnant or breastfeeding individuals; people under 18; people with active or recent cancer (ERRα participates in some cancer-metabolism pathways); people with known cardiovascular disease, arrhythmia, or uncontrolled hypertension (chronic high-dose human data do not exist); people with significant liver or kidney impairment; people on stimulants, hormone modulators, or experimental metabolic compounds without clinician oversight; competitive athletes subject to WADA testing (ERR agonists fall under WADA class S4.5 metabolic modulators as a class, even though SLU-PP-332 is not separately named).
    • Because SLU-PP-332 has no human safety profile, any research planning that involves human exposure should be done under qualified clinician oversight. PDP does not provide medical advice, and nothing on this page substitutes for individualized clinical evaluation.

    Factors noted in the research literature; not patient-specific medical advice.

    Regulatory Status

    Regulatory status

    RUO

    Research Use Only. PeptiJournal supports private research documentation and calculation support. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.

    Comparisons

    Comparisons

    CompoundMechanismRouteStatus
    SLU-PP-332thisA synthetic pan-agonist of estrogen-related receptors (ERR alpha/beta/gamma) studied for activation of an aerobic-exercise-like gene program and increased oxidative metabolism.—Investigational / RUO
    SurvodutideAn investigational long-acting dual agonist of GLP-1 and glucagon receptors studied for appetite regulation and increased energy expenditure.subcutaneousInvestigational / RUO
    TirzepatideActivates both GIP and GLP-1 receptors, providing synergistic effects on insulin secretion, glucose control, and appetite regulation.subcutaneousInvestigational / RUO
    5-Amino-1MQInhibits nicotinamide N-methyltransferase (NNMT), increasing NAD+ availability and enhancing mitochondrial metabolism.oral, subcutaneousInvestigational / RUO
    AdipotideA peptidomimetic that targets prohibitin on the vasculature of white adipose tissue and delivers a pro-apoptotic sequence, studied for selective reduction of fat-tissue blood supply.subcutaneousInvestigational / RUO
    SNAP-8A synthetic acetylated octapeptide (an extended Argireline analog) studied for topical reduction of muscle contraction by interfering with SNARE-complex formation at the neuromuscular junction.subcutaneousInvestigational / RUO
    SS-31A mitochondria-targeted tetrapeptide that selectively binds cardiolipin in the inner mitochondrial membrane, stabilizing electron-transport-chain organization and reducing reactive oxygen species.subcutaneousInvestigational / RUO

    Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.

    FAQ

    Frequently asked questions

    Research-use notice

    Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.

    Cited guide source: View source

    How these protocol references are compiled·About this library