GHK-Cu

GHK-Cu (also written GHK Cu, or copper tripeptide-1) is a copper-binding tripeptide: glycyl-L-histidyl-L-lysine (Gly-His-Lys) holding a single copper ion in the copper(II) state. GHK was originally isolated from human plasma, where it co-purified with roughly equimolar copper, and the free peptide readily forms a complex with Cu(II) (Pickart et al., 1980; Maquart et al., 1988). Since the 1980s the complex has been studied in fibroblast culture, rodent wound-healing models, gene-expression screens and formulation research.

PubChem draws CID 71587328 as a singly charged cation (C₁₄H₂₃CuN₆O₄⁺, 402.92 g/mol); the formula above is the neutral complex, the free GHK peptide less two protons plus one Cu(II) ion.

Published work on GHK-Cu falls into six areas. Each summary below states the model used.

Copper binding and structure

Early cell-culture work showed that GHK readily forms a complex with copper(II) and increases copper uptake into cultured hepatoma cells. The authors noted that its histidyl-lysyl arrangement resembles the copper transport site of albumin (Pickart et al., 1980). Structural work later found the complex dimeric in the crystal but monomeric in solution, with copper held by the N-terminal amine, a backbone amide nitrogen and the histidine imidazole (Hureau et al., 2011). Calorimetry measured predominantly 1:1 binding, with a conditional dissociation constant of about 7.0 × 10⁻¹⁴ M at pH 7.4 (Trapaidze et al., 2012).

Collagen and matrix synthesis in cell culture

In fibroblast cultures, GHK-Cu stimulated collagen synthesis beginning between 10⁻¹² and 10⁻¹¹ M and peaking near 10⁻⁹ M, independent of any change in cell number. The authors pointed out that the Gly-His-Lys triplet occurs in the α2(I) chain of type I collagen (Maquart et al., 1988). In normal human fibroblasts, a follow-up study reported a biphasic rise in sulfated glycosaminoglycan synthesis, mainly dermatan sulfate and cell-layer heparan sulfate, with no change in hyaluronic acid (Wegrowski et al., 1992).

Rodent wound-healing (wound-chamber) models

In rats fitted with implanted wound chambers, GHK-Cu produced concentration-dependent increases in dry weight, DNA, total protein, collagen and glycosaminoglycans. It raised type I and type III collagen mRNA without changing TGF-β mRNA, and a control tripeptide had no significant effect (Maquart et al., 1993). In the same model, a later study tracked matrix metalloproteinases over 22 days and found that GHK-Cu increased pro- and active MMP-2 during the late remodeling phase (Siméon et al., 1999).

Gene-expression studies

A study of lung tissue from smokers with COPD identified 127 genes tied to regional emphysema severity, then used the Connectivity Map to search for compounds that reverse that signature, and identified GHK. In cultured human fibroblasts, GHK reproduced TGF-β-induced expression patterns and organized the actin cytoskeleton. It also restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs (Campbell et al., 2012). The compound tested in this study was the tripeptide GHK.

Inflammation and oxidative stress models

In LPS-stimulated RAW 264.7 macrophages and in mice with LPS-induced acute lung injury, GHK-Cu lowered reactive oxygen species, TNF-α and IL-6, raised superoxide dismutase activity and suppressed NF-κB p65 and p38 MAPK signaling. Lung tissue showed less inflammatory cell infiltration (Park et al., 2016).

Formulation, stability and speciation

Preformulation work found GHK-Cu highly hydrophilic (log D of about -2.4 between pH 4.5 and 7.4) and susceptible to hydrolytic cleavage under basic and oxidative stress, with histidine among its degradation products (Badenhorst et al., 2016).

Liposome carriers for topical cosmetic products have also been studied, with encapsulation efficiencies of roughly 20 to 32 percent for the best-performing carriers (Dymek et al., 2023). A 2026 review argues that much of the literature handles GHK-Cu as one defined substance even though coordination state and labile copper vary with formulation, and that controlled clinical evidence remains sparse (Mateescu et al., 2026).