GHK-Cu
aka Copper Tripeptide-1, Glycyl-L-Histidyl-L-Lysine Copper
Class Matrikine peptide / copper chelate / epigenetic modulator
Status OTC (topical cosmetics); grey-market injectable
TL;DR
Naturally occurring human tripeptide-copper complex that declines ~60% between ages 20–60. Reprograms 31% of the human genome at physiological concentrations — the most broadly genomic effect of any compound in this stack. Bidirectional tissue remodeler: builds organized collagen AND dissolves scar tissue. SIRT1 direct activator → PGC-1α → mitochondrial biogenesis. Essential companion for GLP-1 protocols (prevents skin laxity) and makes BPC-157 safer by suppressing the FAK/paxillin pathway BPC-157 activates.
Key Facts
| Genomic reach | Alters 4,000+ genes (31.2% of human genome) at 1 nM–1 μM |
| Mechanisms | SIRT1 activation; NF-κB suppression; collagen/elastin synthesis; FAK-paxillin suppression (anti-metastatic) |
| Dosing | SubQ 1–2 mg/day (5-on/2-off cycle); topical 0.05–2% skin, 5–6% scalp |
| Key risk | Wilson’s disease = absolute contraindication; zinc depletion with sustained use |
| Key benefit | Anti-cancer (not pro-cancer); skin tightening for GLP-1 users; SIRT1 enzyme expression ↑ |
Mechanism
-
Genomic Reprogramming (core)
- 59% of altered genes upregulated, 41% downregulated
- Pattern: ↓ inflammation/senescence/cancer; ↑ repair/antioxidant/DNA maintenance
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SIRT1 → PGC-1α → Mitochondrial Biogenesis
- Direct SIRT1 binding (Glu230 + Asn226) confirmed 2023–2025
- Same pathway as caloric restriction / resveratrol — but GHK-Cu increases enzyme expression itself
- Synergistic with NMN/NR: those provide NAD+ substrate; GHK-Cu increases SIRT1 enzyme
-
Anti-Metastatic (opposite of BPC-157)
- Suppresses FAK-paxillin — blocks cancer cell migration
- Forces apoptosis in cancer cell lines at 1–10 nM
- 6/12 caspase genes upregulated
-
ECM Remodeling
- Upregulates MMP-1 + MMP-2 (dissolves scar collagen) AND TIMP-1 + TIMP-2 (prevents over-digestion)
- Decorin → basket-weave collagen pattern, not parallel scar bundles
Key Stacks
| Stack | Rationale |
|---|---|
| + BPC-157 | GHK-Cu is the safety counterbalance: suppresses FAK-paxillin BPC-157 activates; builds ECM around BPC’s vessels |
| + Retatrutide | Essential — rapid fat loss causes skin laxity; GHK-Cu upregulates elastin + collagen to re-tighten |
| + SLU-PP-332 | Both drive PGC-1α via SIRT1; GHK-Cu upregulates SOD/catalase/GPX to handle SLU’s ROS output |
| + NAD+ precursors (NMN/NR) | Substrate (NMN) + enzyme (GHK-Cu) both optimized = maximum SIRT1 cascade |
| + Noopept Semax Selank | Noopept/Semax ↓ IL-6 → ↓ CD38 → less NAD degradation → NMN more efficient |
Safety Notes
- Wilson’s disease: Absolute contraindication — copper accumulates fatally
- Zinc depletion: Monitor + supplement zinc during sustained systemic use
- Injectable stinging: Dilute or co-inject with BPC-157 (neutralizes pH)
- Cycling mandatory: 5-on/2-off micro-cycle or 4–8 week on / 2–4 week off macro-cycle
Links
- Peptides MOC
- Genomic Remodeling (mechanism)
- Tissue Repair (mechanism)
- BPC-157 (safety counterbalance)
Source: Gemini Deep Research · Broad Institute cMap · Campbell et al. COPD reversal (2012) · GHK-Cu SIRT1 docking (2023–2025) · PeptideDosages.com 2026-03-20