SLU-PP-332
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Synthetic pan-ERR agonist (estrogen-related receptor alpha/beta/gamma) that mimics exercise-induced metabolic adaptations including muscle fiber type switching, fat oxidation, and enhanced endurance — the "exercise in a pill" compound.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | "Exercise in a Pill" (media), ERR pan-agonist |
| Category | Exercise Mimetic / Metabolic |
| Sequence | N/A (small molecule, not a peptide) |
| Molecular Weight | ~547 Da |
| Molecular Formula | C31H29NO6S |
| PubChem CID | 71245288 |
| Administration | Oral |
| Typical Dose Range | 500 mcg (commercial); HED ~280 mg/day (from mouse data) |
| Half-Life | Not well characterized in humans |
| Storage | Room temperature; protect from moisture and light |
| FDA Status | Research only (preclinical; no human trials) |
| WADA Status | Not specifically listed; metabolic modifier (likely to be added) |
Mechanism of Action
SLU-PP-332 is a potent synthetic agonist of the estrogen-related receptor (ERR) family — ERRalpha, ERRbeta, and ERRgamma — orphan nuclear receptors that serve as master regulators of mitochondrial biogenesis and oxidative metabolism. Despite the name, ERRs do not bind estrogen and are constitutively active transcription factors.
The primary target, ERRalpha (EC50 ~98 nM), activates PGC-1alpha co-activation, the master regulator of mitochondrial biogenesis. This triggers a cascade of metabolic gene expression changes that normally occur with exercise training: upregulation of fatty acid oxidation enzymes (CPT1, HADH), mitochondrial OXPHOS components, and slow-twitch muscle fiber programming (PMID: 36988910). The effects are ERRalpha-dependent, as demonstrated by genetic knockout experiments.
ERRbeta/gamma agonism promotes oxidative (type IIa) skeletal muscle fiber programming at the expense of glycolytic (type IIb) fibers — the same fiber type switching that occurs with endurance training. In mice, SLU-PP-332 treatment significantly increased treadmill running time, demonstrating functional exercise capacity enhancement (PMID: 36988910).
At the whole-body level, SLU-PP-332 increased energy expenditure, enhanced fatty acid oxidation, reduced fat mass (without affecting lean mass), and improved insulin sensitivity in diet-induced obese mice (PMID: 37739806). Additionally, pan-ERR agonism has shown cardiac-protective effects by restoring fatty acid oxidation capacity in failing hearts (PMID: 37961903).
Critical dosing consideration: Mouse studies use ~50 mg/kg/day, which translates to a human equivalent dose of ~280 mg/day for a 70 kg adult. Commercial capsule products (500 mcg) provide approximately 500-1000x less than the HED. Clinical efficacy at supplement doses is unproven.
Key Research Areas
- Exercise mimicry — Muscle fiber type switching and endurance enhancement without exercise (PMID: 36988910)
- Metabolic syndrome — Fat mass reduction, insulin sensitization, glucose tolerance improvement in obese mice (PMID: 37739806)
- Cardiac protection — ERRgamma-mediated restoration of cardiac fatty acid metabolism in heart failure (PMID: 37961903)
- Mitochondrial biogenesis — PGC-1alpha-dependent upregulation of mitochondrial function
- Anti-doping — In vitro metabolite characterization for detection purposes (emerging literature)
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 0 | No human trials conducted |
| Human observational | 0 | No human data |
| Animal in vivo | 3 | Exercise capacity, metabolic syndrome, heart failure models |
| In vitro | 2+ | Receptor binding, metabolite identification |
| Systematic reviews | 0 | Too early |
Clinical Applications
- Weight Management — Metabolic fat loss (preclinical evidence only)
- Metabolic Syndrome — Insulin sensitization and glucose tolerance (preclinical)
- Sarcopenia — Muscle fiber type optimization (preclinical)
- Cardiovascular Health — Cardiac metabolic support (preclinical)
Protocols Using This Peptide
- Weight Loss Protocol (as adjunct)
- Metabolic Reset Protocol (as adjunct)
Ageless Peps Products
- AP-SLUPP332-Capsules — SLU-PP-332 500mcg x 60 capsules
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| IP (mouse) | 50 mg/kg/day | Daily | 4-8 weeks | PMID 37739806, 36988910 |
| Oral (HED) | ~280 mg/day | Daily | N/A | Calculated from mouse dose |
| Oral (commercial) | 500 mcg | Daily | Ongoing | AP capsule (500-1000x below HED) |
Cycling
No validated cycling protocols exist. Preclinical studies used continuous daily dosing. Given the lack of human data, conservative use with periodic breaks is prudent. Some practitioners suggest 8 weeks on / 4 weeks off.
Contraindications & Safety
- Contraindications: No human data; theoretical concerns for hormone-sensitive cancers (ERR activity in tumor biology), pregnancy
- Common side effects: Unknown in humans; no adverse effects reported at preclinical doses in mice
- Drug interactions: Unknown; theoretical interactions with estrogen receptor modulators or metabolic drugs
- Pregnancy/nursing: Contraindicated (no safety data)
- Special populations: No data for any special population. The compound is preclinical.
- Important note: All published efficacy data is from a single research group (Burris lab, originally Washington University in St. Louis, now University of Florida). Independent replication is needed.
Synergistic Combinations
- MOTS-C + SLU-PP-332 — Dual exercise mimetic mechanisms: mitochondrial-derived peptide + ERR nuclear receptor agonism
- 5-Amino-1MQ + SLU-PP-332 — NNMT inhibition + ERR agonism for metabolic syndrome
- AOD-9604 + SLU-PP-332 — Direct lipolysis + metabolic reprogramming
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-37739806 – SLU-PP-332 Alleviates Metabolic Syndrome | Synthetic ERR agonist alleviates metabolic syndrome | 2024 | Animal in vivo |
| PMID-36988910 – SLU-PP-332 ERR Agonist Acute Exercise Response | ERR agonist induces acute aerobic exercise response | 2023 | Animal in vivo |
| PMID-37961903 – Pan-ERR Agonists Ameliorate Heart Failure | Pan-ERR agonists ameliorate heart failure | 2024 | Animal in vivo |
References
- PMID 37739806 — Kim et al., J Pharmacol Exp Ther 2024 (metabolic syndrome)
- PMID 36988910 — Kim et al., ACS Chem Biol 2023 (exercise response)
- PMID 37961903 — Teng et al., Circ Res 2024 (heart failure)
Related
FDA Disclaimer: The products and claims made about specific products have not been evaluated by the United States Food and Drug Administration and are not approved to diagnose, treat, cure, or prevent disease.
Research Purposes Only. SLU-PP-332 is a preclinical research compound with NO human safety or efficacy data. All evidence is from animal studies by a single research group. Commercial doses are 500-1000x below the human equivalent of effective preclinical doses.
#peptide #exercise-mimetic #metabolic #weight-loss #oral #small-molecule #preclinical