LongevityCompound overview
GHK-Cu: what the research literature shows
GHK is the tripeptide glycyl-L-histidyl-L-lysine, a peptide from human plasma that binds copper(II) with high affinity.12 Its copper complex, GHK-Cu, has been studied since 1980 in solution chemistry, fibroblast cultures and animal wound models, and PubChem records the cosmetic ingredient name Copper Tripeptide-1 for it.3456 This page sets out what those studies report and how little of the evidence comes from controlled trials in people.
Evidence cited on this page
- 7 cell studies
- 3 animal studies
- 3 human studies
- 2 reviews
- 3 chemistry studies
- 7 other sources
On this page9 sections
Key points
- GHK is the tripeptide Gly-His-Lys; a 1973 paper reported a tripeptide in human serum, and GHK-Cu is the peptide’s complex with copper(II).17
- Chemistry study In solution three nitrogen atoms of the peptide hold one copper ion, leaving a fourth, exchangeable position.2
- Cell study Fibroblast cultures exposed to the complex made more collagen and more of the matrix enzyme MMP-2.48
- Animal study Rat and rabbit wound models reported more matrix or smaller wounds; a model in irradiated rats found no difference.5910
- Human study Controlled human trials are few, all tested preparations applied to skin or wounds, and they disagree.111213
- No product listing it as an active ingredient was found in Health Canada’s Drug Product Database or the FDA’s Drugs@FDA data on 8 October 2026.1415
What it is
A tripeptide found in human serum
Cell study In 1973 Pickart and Thaler described a tripeptide in human serum that prolonged the survival of normal liver cells and stimulated growth in neoplastic liver.7 The peptide is glycyl-L-histidyl-L-lysine, written Gly-His-Lys or GHK (GHL in a 1980 paper from the same first author).13 That paper describes responses in cultured systems that ranged from stimulated growth and differentiation to toxicity.3
Cell study During isolation it travelled with roughly equimolar copper.3 The authors noted that its sequence resembles the copper-transport site of albumin, and reported that it readily forms complexes with copper(II) and raised copper uptake into cultured hepatoma cells.3
Review A later review by Pickart and colleagues describes GHK as present in human plasma, saliva and urine and as declining with age.16
How the peptide holds copper
Chemistry study A 2011 study used X-ray crystallography and several spectroscopic methods to describe the complex as a solid and in solution.2 In solution GHK forms a monomeric complex in which three nitrogen atoms bind the copper(II) ion: an amino group, a deprotonated amide nitrogen and the imidazole ring of histidine.2 The fourth position around the metal is labile: in the crystal a carboxylate oxygen fills it and the complex is a dimer, and the authors probed it in solution by studying ternary complexes with glycine or histidine.2
Chemistry study Earlier titration work found several complex species across the pH range studied, and showed that the lysine side-chain amino group makes the complex more stable than those of two related peptides that lack lysine.1 In equilibrium dialysis the tripeptide competed with albumin for copper(II), holding a little under half of the metal when the two were at equal concentrations.1
Chemistry study In cyclic voltammetry and an ascorbate-oxidation assay the complex was inert at moderate potentials; at a more negative potential it was reduced to copper(I) and released the metal.2
One name, several species
PubChem lists the peptide alone as C14H24N6O4, 340.38 g/mol.17 Its record for the 1:1 copper complex, titled prezatide copper, gives C14H23CuN6O4+ and 402.92 g/mol.6 A separate record describes two peptides bound to one copper ion,18 and one skin study used a diacetate form.19 All three records list “GHK-Cu” as a synonym, so the name alone does not identify the form, or its formula and weight.61718
How it is studied
Most of the work cited on this page sits on the lower rungs described in the guide to evidence levels in peptide research. Cell studies add the complex to fibroblast cultures and measure collagen synthesis, matrix metalloproteinases and their inhibitors.48 Animal studies use a rat wound-chamber model, in which steel mesh cylinders are placed under the skin and their contents later analyzed, open wounds in rabbits, and skin flaps on irradiated rats.5910
Skin-permeation studies mount human skin in diffusion cells and quantify copper by inductively coupled plasma mass spectrometry.19 The peptide is quantified by reversed-phase liquid chromatography, one of the analytical methods for peptides.20
What the literature reports
Fibroblasts and the extracellular matrix
Cell study Maquart and colleagues reported in 1988 that GHK-Cu increased collagen synthesis in fibroblast cultures at picomolar to nanomolar concentrations, independent of any change in cell number.4 They noted that the GHK sequence occurs in the alpha-2 chain of type I collagen and proposed, without measuring it, that proteases might release it at a wound site.4
Cell study In dermal fibroblast cultures the complex raised levels of matrix metalloproteinase-2 (MMP-2), an enzyme that breaks down matrix proteins, and of two metalloproteinase inhibitors, TIMP-1 and TIMP-2.8 The MMP-2 effect was reproduced by copper ions alone but not by the peptide alone, so in that assay the signal followed the metal.8
Wound models
Animal study In the rat wound-chamber model, chambers that received GHK-Cu accumulated more dry weight, DNA, total protein, collagen and glycosaminoglycan than chambers that received saline, in a concentration-dependent way.5 Messenger RNA for type I and type III collagen rose and that for TGF-beta did not, and a control tripeptide had no significant effect.5
Animal study In a study of eighteen rabbits with full-thickness open wounds, a topical tripeptide-copper complex was compared with zinc oxide and with no treatment.9 Unhealed wound area was smaller than in untreated animals at each follow-up measurement and smaller than in the zinc oxide group only at the first, and granulation tissue covered the wound bed sooner than in either other group.9
Animal study In rats whose skin was irradiated before surgery, flaps that received a GHK-Cu gel did not differ significantly from ointment controls in ischemic area, blood vessel number or area, or VEGF staining.10
Gene-expression studies
Cell study Campbell and colleagues profiled 64 tissue samples from eight lungs of smokers with chronic obstructive pulmonary disease and found 127 genes whose expression tracked the regional severity of emphysema.21 Querying the Connectivity Map, they identified GHK as a compound whose profile ran opposite to that signature.21 In culture, human fibroblasts exposed to GHK, the peptide and not the copper complex, showed expression patterns like those induced by TGF-beta, and fibroblasts from diseased lungs regained collagen-gel contraction.21
Review A review by Pickart and colleagues goes further, stating that GHK can raise or lower the expression of at least 4,000 human genes; its abstract gives no basis for the figure.16 That review shares an author with the 1973 report, and a change in an expression profile is not a demonstrated effect in a living person.716
Topical formulations and skin permeation
Chemistry study A preformulation study for dermal delivery found a strongly negative octanol-buffer distribution coefficient across the pH range tested, which marks the complex as highly hydrophilic.20 Under stress testing the peptide was cleaved in basic and oxidative conditions, and less so in acid, with histidine among the breakdown products.20
Cell study Two laboratory studies on human skin reached different conclusions under different conditions.1922 Hostynek and colleagues kept a large reservoir of the complex on the skin and measured copper, not the intact peptide; copper crossed dermatomed skin over 48 hours and was also retained in the tissue.19 Li and colleagues measured both and reported that almost no peptide or copper crossed intact human skin in nine hours, while skin first pierced with a polymer microneedle array let both through.22
Review A 2026 review found that delivery studies usually report particle size, encapsulation efficiency and bulk release, but seldom resolve whether what is released is intact GHK-Cu, copper-free GHK or free copper.23
Human evidence
Human study Human evidence for GHK-Cu is thin. The three controlled trials cited here all tested preparations applied to skin or wounds; none tested any other use.111213
Human study A multicentre, randomized, evaluator-blinded study compared a GHK-copper gel with vehicle (the gel without the complex) in people with diabetic neuropathic ulcers, all of whom received standardized wound care.11 Median percentage closure of plantar ulcers, those on the sole of the foot, was higher with the gel than with vehicle, and infections were less frequent in plantar ulcers that received the gel straight after the initial debridement (removal of dead tissue).11 The abstract does not give the number of patients.11
Human study A randomized, evaluator-blinded trial in venous stasis ulcers, with 86 evaluable patients, found no difference between a tripeptide-copper cream and placebo.12 Silver sulfadiazine cream reduced ulcer size more than either.12
Human study In a randomized study that 13 patients completed after carbon dioxide laser resurfacing around the mouth, blinded evaluators and computer analysis found no significant difference in redness, wrinkles or overall skin quality between skin-care regimens with and without GHK-Cu.13 Patients’ own questionnaire ratings of the change in skin quality were higher in the GHK-Cu group.13
Review The 2026 review judged the clinical evidence sparse and below current standards for defining the active substance, and described the historical cosmetic reports as small or incompletely characterized.23
Regulatory status
PubChem lists prezatide as a synonym for the peptide.17 On 8 October 2026 Health Canada’s Drug Product Database returned no product with prezatide, or with any ingredient name containing “tripeptide” or “GHK”, as an active ingredient.14 On the same date the FDA’s Drugs@FDA data returned no approved application with prezatide as an active ingredient.15 Cosmetic and natural health product rules were not checked for this page.
The FDA’s page on bulk drug substances that may present significant safety risks in compounding, current as of 22 April 2026, lists GHK-Cu for injectable use among substances previously in category 2 of its interim compounding policies whose nominations were withdrawn.24 The entry says that compounded injectable drugs containing GHK-Cu may pose a risk of immunogenicity because of possible aggregation and peptide-related impurities, and that human data on safety are limited.24
ClinicalTrials.gov lists a phase 2, randomized, double-blind, vehicle-controlled study of a GHK-Cu gel on standardized acute skin wounds in healthy adults, sponsored by Hudson Biotech.25 It was shown as recruiting, with no results posted, on 8 October 2026.25
Products on this site are sold for laboratory research use only, as set out in the research use only policy.
In the laboratory
Horizon supplies GHK-Cu as a lyophilized (freeze-dried) powder in sealed vials. The compound also appears in two cream formulations and in the Glow blend with BPC-157 and TB-500. None of the studies cited on this page tested those formulations or that combination.
Three findings bear on bench work:
- Chemistry study The peptide was stable for at least two weeks at elevated temperature in water and mildly acidic to neutral buffers, and broke down under basic and oxidative stress.20
- Chemistry study Other ligands share the copper: glycine and histidine form ternary complexes with GHK-Cu, and albumin competes for the metal.12
- Review The 2026 review describes the coordination state and speciation of GHK-Cu as dependent on formulation.23
Breakdown routes are covered in the guide to peptide stability and degradation, and general conditions for keeping lyophilized material in the peptide storage guide. Batch documents, when they exist, are published on the Lab Results page.
Compound facts
| Class | Copper(II) complex of a naturally occurring tripeptide |
|---|---|
| Sequence | GHK |
| Length | 3 amino acids |
| Molecular formula | C14H23CuN6O4+ |
| Molecular weight | 402.92 g/mol |
| CAS number | 89030-95-5 |
| PubChem CID | 71587328 (PubChem, opens in a new tab) |
Formula and molecular weight as listed by PubChem (CID 71587328).
Frequently asked questions
Is GHK the same as GHK-Cu?
Cell study No: GHK is the peptide alone and GHK-Cu is its complex with a copper(II) ion, and PubChem gives them different formulas and weights.617 Studies differ in which form they use: one fibroblast finding was reproduced by copper ions but not by the peptide alone, while the emphysema gene-signature work names GHK.821
Has GHK-Cu been tested in people?
Does GHK-Cu pass through skin?
Is GHK-Cu an approved drug in Canada or the United States?
References
Every record links to its PubMed entry or its source. The label under each one names the kind of work it is.
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Lau SJ, Sarkar B. The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma. Biochem J. 1981.
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Hureau C, Eury H, Guillot R, et al. X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties. Chemistry. 2011.
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Pickart L, Freedman JH, Loker WJ, et al. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980.
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Maquart FX, Pickart L, Laurent M, et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. 1988.
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Maquart FX, 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 Clin Invest. 1993.
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PubChem, U.S. National Library of Medicine. Prezatide copper (Copper Tripeptide-1), PubChem compound record CID 71587328. Accessed 8 October 2026.
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Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nat New Biol. 1973.
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Siméon A, Emonard H, Hornebeck W, et al. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sci. 2000.
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Cangul IT, Gul NY, Topal A, et al. Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits. Vet Dermatol. 2006.
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Parker NP, Ardeshirpour F, Schmechel SC, et al. Effects of topical copper tripeptide complex on wound healing in an irradiated rat model. Otolaryngol Head Neck Surg. 2013.
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Mulder GD, Patt LM, Sanders L, et al. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair Regen. 1994.
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Bishop JB, Phillips LG, Mustoe TA, et al. A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. J Vasc Surg. 1992.
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Miller TR, Wagner JD, Baack BR, et al. Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin. Arch Facial Plast Surg. 2006.
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Health Canada. Drug Product Database online query (active ingredient searches for prezatide, tripeptide, copper tripeptide, glycyl and GHK, run through the database's public API; no products returned). Accessed 8 October 2026.
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U.S. Food and Drug Administration. Drugs@FDA data, openFDA drugsfda endpoint (active ingredient searches for prezatide, prezatide copper, tripeptide and GHK; no matches). Accessed 8 October 2026.
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Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015.
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PubChem, U.S. National Library of Medicine. Glycyl-L-histidyl-L-lysine (synonym: prezatide), PubChem compound record CID 73587. Accessed 8 October 2026.
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PubChem, U.S. National Library of Medicine. Bisprezatide copper, PubChem compound record CID 9831891. Accessed 8 October 2026.
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Hostynek JJ, Dreher F, Maibach HI. Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy. Inflamm Res. 2010.
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Badenhorst T, Svirskis D, Wu Z. Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery. Pharm Dev Technol. 2016.
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Campbell JD, McDonough JE, Zeskind JE, et al. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Med. 2012.
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Li H, Low YS, Chong HP, et al. Microneedle-Mediated Delivery of Copper Peptide Through Skin. Pharm Res. 2015.
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Mateescu DM, Gavrilescu DM, Mincioaga RI, et al. GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap. Pharmaceutics. 2026.
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U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 22 April 2026). Accessed 8 October 2026.
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ClinicalTrials.gov, U.S. National Library of Medicine. Topical GHK-Cu Gel for Acute Skin Wound Healing (NCT07437586; status recruiting, no results posted). Accessed 8 October 2026.
Written by Horizon Peptides editorial. Checked against its sources on .
For laboratory research
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