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▎What is GHK CU?
GHK CU is a complex formed by the binding of a tripeptide—composed of glycine (Gly), histidine (His), and lysine (Lys) linked by peptide bonds—to divalent copper ions (Cu⊃2;⁺). Within its chemical structure, the imidazole ring of the histidine residue forms a stable coordinate bond with the copper ion, creating a coordination compound with a specific spatial conformation and biological activity.
▎GHK CU Structure
Source: PubChem | Sequence: Gly-His-Lys Molecular Formula: C28H46CuN12O8 Molecular Weight: 742.3g/mol CAS Number: 130120-56-8 PubChem CID: 9831891 Synonyms: Bisprezatide copper;DL1TR6W6VM |
▎Molecular Background
GHK (glycyl-L-histidyl-L-lysine) is a tripeptide composed of glycine (Gly), histidine (His), and lysine (Lys). The histidine-containing sequence can coordinate divalent copper ions (Cu⊃2;⁺), giving rise to copper-associated GHK species commonly described in the literature as GHK-Cu. PubChem contains more than one record associated with the terms “GHK-Cu” and “copper tripeptide,” reflecting differences in deposited stoichiometry, protonation state, and structural representation. For this reason, GHK-Cu is best treated as a coordination-complex designation unless the exact chemical form is defined for a particular experiment[1,12–14].
Research Progress
Maquart et al. investigated GHK-Cu in an implanted wound-chamber model in Sprague-Dawley rats. The study used several experimentally defined concentrations and measured dry weight, total protein, collagen, DNA, and glycosaminoglycan content in recovered tissue samples. Under the conditions of this animal model, the authors reported increases in several of the measured connective-tissue parameters[2].
Abdulghani et al. conducted a one-month comparative study involving twenty participants to examine ultrastructural changes associated with four topical formulations containing GHK-Cu, melatonin, vitamin C, or retinoic acid. Ten participants applied formulations containing GHK-Cu and melatonin to opposite thighs, while the remaining participants applied formulations containing vitamin C and retinoic acid. Skin biopsies were collected at baseline and after the one-month study period. The authors reported increased procollagen synthesis by dermal papillary fibroblasts in 70% of participants in the GHK-Cu group, compared with 50% in the vitamin C group and 40% in the retinoic acid group. Because this was a small comparative study, the findings should be interpreted within the limits of its sample size and design[3].
Hostynek et al. evaluated the permeation of GHK-Cu across human stratum corneum (SC), whole epidermis (SC plus viable epidermis), and split-thickness skin in vitro. Using inductively coupled plasma mass spectrometry, the authors reported skin permeability coefficients (Kp) over 48 hours ranging from 3 × 10⁻⁷ cm/h across heat-separated epidermis to 5.5 × 10⁻⊃3; cm/h across isolated stratum corneum. Copper measured in the receptor phase represented approximately 0.006% of the applied dose for the epidermal membrane, 20% for isolated stratum corneum, and 2% for split-thickness skin. The study also reported substantially greater copper retention in isolated stratum corneum than in split-thickness skin. The authors noted that the high apparent transport across isolated stratum corneum should be interpreted in light of the absence of deeper skin layers in that model[4].
Park et al. used a Franz diffusion cell with a phosphate-buffered saline receptor phase to compare GHK, GHK-Cu, and Pal-GHK across a synthetic epidermal membrane (Neoderm-E®) over 24 hours. The reported cumulative permeation was 4.61% for Pal-GHK, 3.86% for GHK-Cu, and 2.53% for GHK. These results describe transport through the synthetic membrane used in the experiment and should not be interpreted as a direct measure of in vivo human skin exposure[5].
Chen et al. developed a multifunctional Gel/ODex/MT/GHK-Cu hydrogel system using dynamic Schiff-base cross-linking between gelatin (Gel) and oxidized dextran (ODex), together with MXene@TiO₂ (MT) heterojunction nanosheets and GHK-Cu as functional components. The authors reported rheological, self-healing, adhesion, and swelling characteristics for the combined material. Under 808-nm near-infrared irradiation, the MT-containing system reached temperatures above 45°C within 15 minutes, and the study reported greater than 99% bacterial ablation for Staphylococcus aureus and Escherichia coli under the tested photothermal conditions. Cell-based experiments included redox-related and endothelial-cell migration endpoints, while a mouse full-thickness skin-defect model was used to assess wound-closure, epithelialization, collagen-deposition, and hair-follicle-related endpoints. Because GHK-Cu was one component of a multi-component hydrogel, the reported findings describe the complete experimental system and should not be attributed to GHK-Cu alone[6].

Fig. 1. (a) Schematic illustration of the preparation of ODex and the Gel/ODex/MT/GHK-Cu hydrogel. (b) Experimental functions evaluated for the combined hydrogel system in the cited study[6].
Jeon et al. formulated a complex of Torilis japonica extract (TJE) and GHK-Cu and evaluated it in a TNF-α/IFN-γ-stimulated HaCaT keratinocyte model. The study measured the atopic-dermatitis-associated chemokines TARC/CCL17 and CTACK/CCL27, IgE-related responses, transcription of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13, and keratinocyte migration. The authors reported changes in these endpoints, with the 6:4 TJE:GHK-Cu condition producing the largest effects among the tested formulations in their in vitro system. These findings are specific to the cell model and combination evaluated in the study[7].

Fig. 2. Th2 cytokine gene-expression endpoints reported for TJE and the TJE–GHK-Cu complex in TNF-α/IFN-γ-stimulated HaCaT cells. Relative mRNA expression of IL-4, IL-5, IL-10, and IL-13 was quantified by RT-qPCR and normalized to β-actin. Data and statistical annotations are reproduced from the cited in vitro study[7].
Tucker et al. evaluated GHK-Cu in a 5xFAD transgenic mouse model used to study amyloid-related neurodegeneration. Over the experimental period, the investigators assessed behavioral performance, amyloid-plaque burden, and inflammatory endpoints in the brain. The authors reported differences between the GHK-Cu and saline groups in selected cognitive, amyloid-associated, and inflammatory measures. These observations were generated in a preclinical mouse model and do not establish comparable effects in humans[8].
In a separate study in aged C57BL/6 mice, Tucker et al. examined spatial-memory and learning-navigation tasks together with markers related to neuroinflammation and axonal damage. Relative to saline controls, the authors reported higher performance on selected behavioral tasks and lower expression of selected markers in the GHK-Cu group. This work remains preclinical and should be interpreted within the conditions of the animal model[9].

Fig. 3. Immunohistochemistry endpoints in the frontal cortex from the cited aged-mouse study, including MCP-1, IBA-1, and NFL-1 staining intensities. Statistical annotations and cohort information are reproduced from the original preclinical figure[9].
Park et al. evaluated GHK-Cu in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and in an LPS-induced mouse model. In the cell experiments, the authors reported changes in NF-κB p65 and p38 MAPK signaling, reactive oxygen species (ROS), superoxide dismutase (SOD) activity, TNF-α, and IL-6. In the mouse model, histologic lung-injury and inflammatory-cell-infiltration endpoints differed among the experimental groups. These observations were generated under defined preclinical conditions[10].

Fig. 4. Experimental design, representative lung sections, and lung-injury scoring from the cited LPS-induced mouse study. Group assignments, doses, scale bars, and statistical annotations are reproduced from the original preclinical figure[10].
Research Limitations
GHK-Cu should not be assumed to represent one chemically invariant species under all experimental conditions. In aqueous systems, copper coordination can shift with factors such as pH, metal-to-ligand ratio, counterions, buffer composition, and other formulation variables. PubChem likewise contains multiple deposited records associated with GHK-Cu or copper-tripeptide representations. A recent review emphasizes that coordination state, speciation, stability, and toxicity may depend strongly on formulation conditions[1,12–14].
Published GHK/GHK-Cu research also has important evidence limitations. In vitro skin-permeation studies do not directly establish exposure in living human tissue, and the available human studies are relatively small and heterogeneous. Large, well-controlled clinical datasets remain limited, while many published findings come from cell, ex vivo, synthetic-membrane, or animal models. For this reason, results from these systems should be interpreted within the design and endpoints of the original study rather than generalized to human outcomes[11].
COCER Peptides presents GHK-Cu for laboratory research use only. It is not intended for human or veterinary use. The research discussed above summarizes findings reported in the cited literature and is not a statement of clinical efficacy or an instruction for use.
▎Relevant Citations
References
[1] Mateescu D, Gavrilescu D, Mincioaga R, et al. GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap[J]. Pharmaceutics, 2026,18(9):1077.
DOI:10.3390/pharmaceutics18091077.
[2] Maquart F, Bellon G, Chaqour B, et al. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds.[J]. The Journal of clinical investigation, 1993,92(5):2368-2376.
DOI:10.1172/JCI116842
[3] Abdulghani A A, Sherr A, Shirin S, et al. Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin[J]. Disease Management and Clinical Outcomes, 1998,1(4):136-141.
DOI:10.1016/s1088-3371(98)00011-4
[4] Hostynek J J, Dreher F, Maibach H I. Human skin penetration of a copper tripeptide in vitro as a function of skin layer[J]. Inflammation Research, 2011,60(1):79-86.
DOI:10.1007/s00011-010-0238-9
[5] Park S I, An G M, Kim M G, et al. Enhancement of skin permeation of anti-wrinkle peptide GHKs using cell penetrating peptides[J]. Korean Chemical Engineering Research, 2020,58(1):29-35.
DOI: 10.9713/kcer.2020.58.1.29
[6] Chen S, Lei M, Liu P, et al. Gelatin-oxidized dextran Schiff base hydrogel with MXene@TiO₂ and GHK-Cu: A multifunctional dressing for photothermal-antibacterial and pro-angiogenic wound repair[J]. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2026,751:141621.
DOI:https://doi.org/10.1016/j.colsurfa.2026.141621.
[7] Jeon S, Maeng J, Lee J, et al. A Torilis japonica Extract–GHK-Cu Complex Attenuates Th2 Cytokines and Promotes Keratinocyte Recovery: A Potential Antioxidant Strategy for Atopic Dermatitis[J]. Antioxidants, 2026,15(7):818.
DOI:10.3390/antiox15070818.
[8] Tucker M, Liao G Y, Keely A, et al. Behavioral and neuropathological features of Alzheimer’s disease are attenuated in 5xFAD mice treated with intranasal GHK peptide[J]. Aging Pathobiology and Therapeutics, 2024, 6(3):102-108.
DOI:10.31491/APT.2024.09.148.
[9] Tucker M, Keely A, Park J Y, et al. Intranasal GHK peptide enhances resilience to cognitive decline in aging mice[J]. bioRxiv, 2023.
DOI:10.1101/2023.11.16.567423.
[10] Park J, Lee H, Kim S, et al. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice[J]. Oncotarget, 2016,7(36):58405-58417.
DOI:10.18632/oncotarget.11168.
[11] Mortazavi S M, Mohammadi Vadoud S A, Moghimi H R. Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective[J]. BioImpacts, 2024,15:30071.
DOI:10.34172/bi.30071.
[12] PubChem. Compound Summary for CID 73587, glycyl-L-histidyl-L-lysine. National Center for Biotechnology Information.
[13] PubChem. Compound Summary for CID 133697840, GHK-Cu. National Center for Biotechnology Information.
[14] PubChem. Compound Summary for CID 139035031, Copper tripeptide. National Center for Biotechnology Information.
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