SLU-PP-332
aka ERR agonist
Class Pan-ERR agonist / exercise mimetic
Status Preclinical / research chemical — biohacking community use only
TL;DR
First compound to directly target the terminal transcriptional effectors of endurance exercise (ERRα/β/γ → PGC-1α), bypassing upstream kinase limitations of older exercise mimetics. In DIO mice: +50% treadmill endurance, −20% fat mass, +50% insulin sensitivity — without changing food intake or activity. Works during immobilization. Biohacking community is ahead of the science. Theoretical cancer risk via ERRα overexpression in aggressive cancers; mandatory cycling required.
Key Facts
| Mechanism | Direct ERRα/β/γ agonism → PGC-1α transcriptional program |
| Preclinical results | +50% endurance, −20% fat mass, +50% insulin sensitivity (DIO mice) |
| Dosing | 1–5 mg/day SubQ (experimental, no established human dose) |
| Cycling | 4–8 weeks on / 4 weeks off (mandatory) |
| Key risk | Theoretical oncogenic (ERRα in breast/prostate cancers); hepatotoxicity at ≥100 mg/kg |
| Key advantage | Works during immobilization — unique in the stack |
ERR Isoforms
| Isoform | EC₅₀ | Primary tissue | Function |
|---|---|---|---|
| ERRα | 98 nM | Skeletal muscle, adipose | Mitochondrial biogenesis, endurance |
| ERRβ | 215 nM | CNS, embryonic | Stem cell pluripotency |
| ERRγ | 340 nM | Heart, kidneys | Cardiac oxidative metabolism |
Mechanism
-
ERR → PGC-1α → Mitochondrial Biogenesis
- Direct nuclear receptor agonism — no upstream kinase bottlenecks
- Upregulates full electron transport chain (Complex I–V)
- ↑ SOD1 (+131%), SOD2 (+45%), Catalase (+61%), GPX1 (+71%)
-
Cardioprotection
- Rescues ejection fraction in heart failure (TAC) model
- Normalizes cardiac metabolites without pathological hypertrophy (via E2F1 suppression)
-
Human Tissue (2025)
- Elderly female myoblasts: ↓NOX4, ↑SIRT1, PGC-1α, FNDC5; ↓SA-β-gal 26.1%
Why Not Cardarine (GW501516)?
| Cardarine | SLU-PP-332 | |
|---|---|---|
| Target | PPARδ | ERR α/β/γ |
| Cancer risk | Abandoned — caused tumors | Theoretical (ERRα in cancers) |
| Mechanism | Blocks apoptosis | Different pathway — no apoptosis blockade |
Key Stacks
| Stack | Rationale |
|---|---|
| + Retatrutide | GCGR-liberated fatty acids → SLU-PP-332 oxidizes them; synergistic fat oxidation |
| + BPC-157 | SLU creates metabolic demand; BPC builds capillary supply to meet it |
| + GHK-Cu | GHK upregulates SOD/catalase/GPX to handle SLU’s increased ROS output |
| + NAD+ precursors | SIRT1 is NAD+-dependent; prevents substrate bottleneck |
| + Glutathione | Manages mtROS from increased OXPHOS; prevents fatigue |
| + Creatine | Buffers ATP from new mitochondria; efficient energy transfer |
Cycling Warning
- Do NOT run continuously — risk of glycogen/nutrient exhaustion
- 4–8 weeks on / 4 weeks off minimum
- Low cholesterol = poor response (nuclear receptors need steroid substrates)
Links
- Peptides MOC
- Exercise Mimetics (mechanism)
- GLP-1 GIP Glucagon — metabolic overlap with Retatrutide
Source: Washington University / UF research · Gemini Deep Research · PeptideDosages.com 2026-03-20