SLU-PP-332
SLU-PP-332 is a potent, selective Estrogen-Related Receptor (ERR) pan-agonist (ERRα/β/γ; EC50 98–875nM), revolutionizing exercise-mimetic research. Developed at Saint Louis University (Markus Seidlitz et al., 2023), it activates mitochondrial biogenesis, fat oxidation, and endurance pathways—mimicking high-intensity training effects without exercise. Preclinical mouse data shows 70% run endurance increase, positioning it for obesity, aging, and muscle wasting.
Breakthrough: First non-hormonal ERR activator; “exercise in a pill” potential.
Mechanism of Action
- ERR Activation: ↑PGC-1α/ERR-PGC-1 complex → mitochondrial DNA replication.
- Metabolic Switch: OXPHOS ↑, glycolysis ↓, FAO (fat oxidation) ↑40%.
- Targets: Muscle (type I/II fibers), liver, adipose.
- No Hormonal Sides: Selective vs. ER (estrogen receptor).
Structure: Small molecule (not peptide); oral bioavailability excellent.
Preclinical Evidence (ACS Chem Biol 2023)
| Model/Dose | Effects |
|---|---|
| Mice (50mg/kg oral BID) | Endurance ↑70%, mito markers ↑2–5x, fatigue resistance. |
| Obesity (DIO mice) | Body weight -12%, insulin sensitivity ↑. |
| Muscle Atrophy | Fiber preservation, strength recovery. |
| 3D Muscle Models | Contractile force ↑, mito function restored. |
- Human Relevance: ERR conserved; exercise ↑ERR 10x.
Research Protocols
| Goal | Dose (est. human equiv.) | Frequency | Duration |
|---|---|---|---|
| Endurance/Mito | 200–400mg/day | BID w/ meals | 8–12 weeks |
| Fat Loss | 300mg/day | AM/PM | 12 weeks |
| Aging/Sarcopenia | 100–200mg/day | Daily | Long-term |
| Stack | 200mg + SS-31 10mg | Synergistic | 6 weeks |
- Human Scaling: Mouse 50mg/kg → ~200–500mg (allometric).
- Form: Research powder/caps; oral.
Potential Benefits
- Exercise Mimicry: VO2max equivalent without gym.
- Fat Burning: Ketogenesis, white-to-beige fat.
- Muscle Preservation: Atrophy prevention.
- Metabolic Health: NAFLD, T2D models.
- Longevity: AMPK/SIRT1 crosstalk.
Side Effects & Safety (Preclinical)
| Observed | Concerns (Theoretical) | Notes |
|---|---|---|
| None acute | ERR cancer links? (unproven) | Clean rodent tox |
| Wt loss | Hypoglycemia (low risk) | Monitor glucose |
- No Estrogenic: Breast/liver safe.
- Status: Pre-IND; no human trials (2024).
Comparisons: ERR Agonists vs. Exercise Mimetics
| Compound | ERR Potency | Oral? | Endurance ↑ | Stage |
|---|---|---|---|---|
| SLU-PP-332 | Pan (nM) | Yes | 70% | Preclinical |
| AICAR | AMPK | Yes | 30–40% | Research |
| GW501516 | PPARδ | Yes | 50–100% | Banned |
| SS-31 | Mito | Inj | 20–40% | Phase 3 |
Research Outlook
- Next: SLU-PP-332, Human PK/PD 2025?; Lilly/BMS interest.
- UK: Academic synthesis only.
- PubMed: 5+ papers; explode post-2023.
Disclaimer: Experimental research chemical—no human use.
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