GHK-Cu: Scientific Profile
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GHK-Cu (glycyl-L-histidyl-L-lysine:copper(II); Copper Tripeptide-1, CAS 89030-95-5): endogenous copper tripeptide for research. It delivers Cu(II) to dermal fibroblasts, activates type I collagen, decorin and glycosaminoglycans, modulates MMP and the TGF-beta pathway; a modulator of more than 4000 genes.
GHK-Cu (glycyl-L-histidyl-L-lysine complexed with copper(II); Copper Tripeptide-1 / prezatide copper; CAS 89030-95-5; formula C14H23CuN6O4) is an endogenous copper tripeptide, discovered in human plasma by Loren Pickart in 1973. Its plasma concentration is ~200 ng/mL in young people and drops to ~80 ng/mL by around age 60. The GHK peptide binds Cu(II) with exceptional affinity (Kd ~10^-16 M), forming a stable complex that transports and delivers bioavailable copper to dermal fibroblasts. Mechanism: it activates the synthesis of type I collagen, decorin and glycosaminoglycans, modulates matrix metalloproteinases (MMP) and the TGF-beta pathway, exhibits SOD-type antioxidant activity and modulates the expression of more than 4000 human genes. In vitro and preclinical research applications: dermal regeneration, wound healing, collagen remodeling and skin senescence. It is distributed as a lyophilized powder for research (RUO). Reconstitution: bacteriostatic or sterile water to the desired working concentration. Storage: -20 degrees C for the lyophilizate; 2-8 degrees C, protected from light, <=30 days once reconstituted. GHK-Cu is not approved as a systemic medicine in humans.
Mechanism of action
GHK-Cu acts through multiple mechanisms: (1) Selective transport and delivery of Cu2+: copper is an essential cofactor for lysyl oxidase (collagen/elastin cross-linking), cytochrome c oxidase, Cu/Zn superoxide dismutase and ceruloplasmin; GHK provides bioavailable Cu2+ without the toxicity of free copper; (2) Stimulation of extracellular matrix synthesis: it increases the expression of COL1A1, COL3A1, decorin, glycosaminoglycans and elastin in dermal fibroblasts; (3) Modulation of metalloproteinases: it increases TIMP-1 and TIMP-2 (tissue inhibitors of MMP), reducing degradation of pre-existing collagen; (4) Activation of follicular dermal papillae: it stimulates hair growth via upregulation of VEGF and noggin; (5) Broad modulation of the transcriptome: gene expression analysis demonstrates modulation of ~4,192 human genes, including partial reversal of transcriptional signatures associated with aging; (6) Antioxidant effects: via supply of Cu2+ to SOD1 and direct modulation of ROS generation; (7) Neuroprotection: increase of NGF and BDNF in in vitro models. Topical half-life: ~6-12 hours in the stratum corneum. Systemic absorption after topical application: <2%.
Mechanism summary
An endogenous copper tripeptide that binds Cu(II) with very high affinity (Kd ~10^-16 M) and delivers it bioavailable to dermal fibroblasts; it activates the synthesis of type I collagen, decorin and glycosaminoglycans, modulates MMP and the TGF-beta pathway, shows SOD-like antioxidant activity and modulates more than 4000 genes.
Clinical Studies (8)
- GHK-Cu in tissue regeneration: new genomic data (Pickart L, Margolina A. · International Journal of Molecular Sciences · 2018) — Broad transcriptomic analysis of the action of GHK-Cu on gene expression in human fibroblasts and keratinocytes. PMID 29986520.
- GHK Peptide as a Natural Modulator of Multiple Cellular Pathways (Pickart L, Margolina A. · BioMed Research International · 2015) — Review of the multiple mechanisms of GHK-Cu in tissue regeneration and anti-aging. PMID 26236730.
- Glycyl-L-histidyl-L-lysine-Cu(2+) rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway (Deng, et al. · Journal of Cachexia, Sarcopenia and Muscle · 2023) PMID 36905132.
- Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. (Miller TR, et al. · Arch Facial Plast Surg · 2006) PMID 16847171.
- Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. (Mulder GD, et al. · Wound Repair Regen · 1994) PMID 17147644.
- Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). (Siméon A, et al. · J Invest Dermatol · 2000) PMID 11121126.
- Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. (Maquart FX, et al. · FEBS Lett · 1988) PMID 3169264.
- In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. (Maquart FX, et al. · J Clin Invest · 1993) PMID 8227353.
Warnings
GHK-Cu is a compound exclusively for research use (RUO); the following warnings and handling considerations apply to its use in the laboratory:
- Systemic use not approved by regulators
- Overexposure to copper can cause accumulation in people with altered metabolism
- Limited clinical data for injectable use
- Possible interaction with copper chelators
- Storage in darkness: UV light degrades the Cu-peptide chelation
- Do not mix with high-concentration vitamin C (reduces Cu2+ to Cu+)
- Hypersensitivity to copper or GHK peptides
- Wilson's disease (alteration of copper metabolism)
- Deep wounds with active bleeding (topical use)
Technical data
- CAS
- 89030-95-5
- Molecular formula
- C14H23CuN6O4
- Molecular weight
- 402.92 Da
- Compound type
- peptide
- Storage
- -20 °C liofilizado; 2-8 °C reconstituido; proteger de la luz
- Shelf life (lyophilized)
- 24 months at 2-8°C in the dark
- Shelf life (reconstituted)
- 7-14 days at 2-8°C in darkness
- Light-sensitive
- Sí
Available for research
GHK-Cu is available as a research reagent (RUO):
Frequently asked questions about GHK-Cu
What is GHK-Cu?
GHK-Cu (glycyl-L-histidyl-L-lysine:copper(II); Copper Tripeptide-1, CAS 89030-95-5): endogenous copper tripeptide for research. It delivers Cu(II) to dermal fibroblasts, activates type I collagen, decorin and glycosaminoglycans, modulates MMP and the TGF-beta pathway; a modulator of more than 4000 genes.
What is the mechanism of action of GHK-Cu?
An endogenous copper tripeptide that binds Cu(II) with very high affinity (Kd ~10^-16 M) and delivers it bioavailable to dermal fibroblasts; it activates the synthesis of type I collagen, decorin and glycosaminoglycans, modulates MMP and the TGF-beta pathway, shows SOD-like antioxidant activity and modulates more than 4000 genes.
What is GHK-Cu investigated for?
In preclinical research, GHK-Cu is studied primarily in: Research on dermal wound healing; Collagen remodeling models; Studies of hair growth. Material exclusively for scientific research.
What are the chemical properties of GHK-Cu?
Molecular formula C14H23CuN6O4; molecular weight 402.92 Da; CAS number 89030-95-5.
How is GHK-Cu stored?
Condiciones de conservación: -20 °C liofilizado; 2-8 °C reconstituido; proteger de la luz; estabilidad liofilizado: 24 meses a 2-8°C en oscuridad; una vez reconstituido: 7-14 días a 2-8°C en oscuridad; protéjase de la luz.
What routes of administration are studied for GHK-Cu?
In the research models the following are described: Topical, Subcutaneous. Use is exclusively for scientific research.