GHK-Cu Research, Specifications & Scientific Information

Introduction

GHK-Cu is the odd one out in a peptide library. It is three residues long — glycine, histidine, lysine — and the part of it that does the chemistry is not the peptide at all but a copper(II) ion held by it. The tripeptide occurs naturally in human plasma and cerebrospinal fluid as one of a small set of recognised copper-chelating motifs, and the same GHK triplet sits inside the alpha-2 chain of type I collagen, which is the origin of the long-standing proposal that proteolysis at a site of tissue damage releases it ^{[5, 1]}. Its research literature is correspondingly shaped: quantitative coordination chemistry, four decades of fibroblast culture work on matrix synthesis, a transcriptional signature identified computationally, and a formulation problem that has never been solved.

What the literature does not contain is a published clinical trial. This page sets out the chemistry, the cell and animal work, and the permeation data, with every source resolved against PubMed, Crossref or ClinicalTrials.gov at the time the page was built. It describes research, not use, and contains no guidance on handling the material.

What Is GHK-Cu?

GHK-Cu is a coordination complex, not a modified peptide. One copper(II) ion is bound by one molecule of glycyl-L-histidyl-L-lysine through the classical N-terminal metal-binding arrangement: the free α-amino group of the glycine, the imidazole nitrogen of the histidine at position 2, and the deprotonated amide nitrogen between them. That arrangement is what the compound is; strip the copper out and a different substance, with its own register entry and its own INN — prezatide — remains.

The chemistry is quantified. Isothermal titration calorimetry with glycine as a weaker competing ligand put the conditional dissociation constant at pH 7.4 at 7.0 ± 1.0 × 10⁻¹⁴ M, with binding predominantly 1:1. The albumin-derived motif DAHK was measured alongside it at 2.6 ± 0.4 × 10⁻¹⁴ M, and the enthalpic and entropic contributions to the two differed ^[5]. A dissociation constant in the tens of femtomolar is extremely tight by the standards of biological metal binding, and it is the single most solid number on this page.

It is not an approved medicine. GHK-Cu has not been approved by the U.S. Food and Drug Administration for any indication. It is widely used as a cosmetic ingredient under the International Nomenclature of Cosmetic Ingredients name copper tripeptide-1, which is a different regulatory category and establishes nothing about what the compound does.

GHK-Cu Specifications

GHK-Cu is not a peptide in the sense that the other entries in this library are; it is a coordination compound, and the copper(II) ion is part of the molecule rather than an additive. The peptide half is the tripeptide glycyl-L-histidyl-L-lysine, three residues, sequence GHK, recorded in PubChem as CID 73587 with CAS 49557-75-7 and UNII 39TG2H631E, molecular formula C14H24N6O4 and average mass 340.4 g/mol; its INN is prezatide. The copper complex is a separate register entry: PubChem records prezatide copper as CID 71587328 with CAS 89030-95-5 and UNII 6BJQ43T1I9. Published molecular formulas and masses for the complex differ from one another because they describe different protonation states and counter-ion arrangements of the same coordination chemistry: PubChem's prezatide copper entry is the cation C14H23CuN6O4+ at 402.9 g/mol, other entries describe an anionic or a bis-ligand form, and the neutral formula C14H24CuN6O4 at 403.9 g/mol is the value carried in the supplier catalog and shown above. A difference of one or two mass units between listings of 'GHK-Cu' is therefore usually a difference in how the complex is written, not a difference in material — which is the opposite of the situation for most compounds in this library, and a reason to read a certificate of analysis for this compound with the copper content in mind as well as the mass. The metal-binding site is the classical N-terminal motif: the free alpha-amino group, the imidazole nitrogen of histidine at position 2, and the deprotonated amide nitrogen between them.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does GHK-Cu Work?

No receptor has been identified, and no receptor is proposed. That is a genuine structural difference from most of this library rather than a gap in the literature: a compound whose defining property is a femtomolar affinity for a metal ion is characterised by what it holds, not by what it switches on.

Two families of explanation appear in the published work, and they are not the same claim.

The first is copper delivery. Copper is a required cofactor for lysyl oxidase, which cross-links collagen and elastin, and for superoxide dismutase, among others. On this account GHK is a carrier, and the biology observed is the biology of making copper available in a particular place at a particular time. The tightness of the binding cuts both ways here: a complex that holds copper at 10⁻¹⁴ M does not release it readily, so "delivery" requires an exchange mechanism rather than dissociation.

The second is transcriptional. A gene-expression signature associated with the compound was identified computationally from a connectivity-mapping analysis and then reproduced in cultured human fibroblasts ^[7]. On this account the relevant effect is a coordinated change in expression across many genes rather than the activation of one pathway — which is what review articles mean when they describe the compound as a modulator of multiple cellular pathways ^{[11, 12]}.

Neither account has been tested in a controlled human study.

GHK-Cu Mechanism of Action

In vitro research

Collagen synthesis in fibroblast culture. In cultured fibroblasts, GHK-Cu stimulated collagen synthesis beginning between 10⁻¹² and 10⁻¹¹ M, reaching a maximum at 10⁻⁹ M, and the stimulation was independent of any change in cell number. The authors noted that a GHK triplet is present in the α2(I) chain of type I collagen and proposed on that basis that the tripeptide might be liberated by proteases at a site of tissue damage ^[1].

Glycosaminoglycan synthesis. In normal human fibroblasts labelled with tritiated glucosamine and ³⁵S sulfate, GHK-Cu increased synthesis of total glycosaminoglycans both secreted into the medium and associated with the cell layer. The concentration response was biphasic: maximal stimulation at 10⁻⁹ to 10⁻⁸ M, with the rate returning progressively toward control at higher concentrations. Electrophoretic analysis showed preferential stimulation of dermatan sulfate ^[2].

The biphasic shape is worth keeping in view. A compound whose effect peaks and then declines as concentration rises cannot be characterised by a single figure, and results obtained at one concentration do not generalise upward.

Transcriptional signature. Gene expression was profiled across 64 lung tissue samples — eight regions from each of eight lungs — from smokers with chronic obstructive pulmonary disease, with regional emphysema severity quantified by mean linear intercept from micro-CT. 127 genes were significantly associated with severity; those falling with increasing destruction were enriched in tissue repair processes including the TGF-β pathway, actin organisation and integrin signalling. Connectivity-Map analysis identified GHK as a compound able to reverse that signature. Treatment of human fibroblasts with GHK then recapitulated TGF-β-induced expression patterns, produced organisation of the actin cytoskeleton, and raised integrin β1 expression; adding GHK or TGF-β restored collagen I contraction and remodelling by fibroblasts derived from COPD lungs relative to fibroblasts from former smokers without COPD ^[7].

TGF-β secretion — in the opposite direction. In normal human dermal fibroblasts, 1 nM GHK, GHK-Cu and free copper ions each decreased IGF-2-dependent TGF-β1 secretion ^[9]. Set beside the Connectivity-Map result, this is a reminder that "affects the TGF-β pathway" is not a direction, and that the two readouts — transcriptional signature and secreted protein — are not the same measurement.

Copper-free GHK in epidermal models. In monolayer cultures of normal human keratinocytes and in skin-equivalent models, copper-free GHK increased keratinocyte proliferation, produced more cuboidal basal cells, gave linear and intense α6 and β1 integrin staining along the basement membrane, and increased the number of p63- and PCNA-positive cells. The authors concluded that copper-free GHK showed effects similar to the copper complex ^[8].

These are observations in cultured cells and in reconstructed tissue models. They establish nothing about animals or people.

What Is GHK-Cu Being Researched For?

Published research on GHK-Cu falls into four groups, which differ sharply in maturity:

• Coordination chemistry. Quantitative measurement of copper(II) binding and of the thermodynamics behind it ^[5]. This is the best-evidenced part of the literature and is settled science.
• Extracellular matrix biology. Collagen and proteoglycan synthesis by fibroblasts in culture and matrix accumulation in rodent wound chambers ^{[1, 2, 3]}.
• Transcriptomics. The emphysema signature work and the review literature built on it ^{[7, 12]}.
• Dermatological and cosmetic formulation. Permeation, encapsulation and delivery, which is where most recent activity sits ^{[10, 13]}.

A fifth area has opened more recently: murine models of ulcerative colitis ^[14].

What is absent is clinical evidence. No randomised or controlled trial of GHK-Cu appears in the indexed literature. One phase 2 trial of a topical gel formulation in acute standardised punch-biopsy wounds, with a planned enrolment of 60, was registered in 2026 and is recruiting ^[15]. Because there is no published human research on this compound, this page carries no human-clinical section; adding one would require material that does not exist.

Preclinical Research on GHK-Cu

Animal research

Rat wound chamber model. Stainless steel wire mesh cylinders were implanted subcutaneously on the backs of rats and injected sequentially with saline or with a range of concentrations of GHK-Cu. Chamber contents were then analysed for dry weight, total protein, collagen, DNA, elastin, glycosaminoglycans, and specific mRNAs. A concentration-dependent increase in dry weight, DNA, total protein, collagen and glycosaminoglycan content was found; stimulation of collagen synthesis was twice that of non-collagen proteins; type I and type III collagen mRNAs rose while TGF-β mRNA did not; and the relative amount of dermatan sulfate increased. A control tripeptide, L-glutamyl-L-histidyl-L-proline, had no significant effect ^[3].

The control tripeptide is the part of that design that gives the result its weight. It rules out the trivial explanation that any small peptide injected into a wound chamber increases matrix accumulation.

Murine colitis. In BALB/c mice given 3% dextran sulfate sodium for 14 days, GHK-Cu improved disease activity index scores, increased goblet cell numbers and suppressed TNF-α, IL-6 and IL-1β. A co-culture of mouse colonic epithelial cells with peritoneal macrophages showed up-regulation of the tight-junction proteins ZO-1 and occludin, and network pharmacology with molecular docking identified SIRT1 as a candidate target, with SIRT1 protein expression raised after exposure ^[14].

Limitations. The wound chamber work dates from 1993 and has not, in the indexed literature, been replicated by an independent group in a modern model. The colitis study is a single 2025 report using a chemically induced model and a computational target prediction rather than a validated target. Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of GHK-Cu Research

In vitro research

The permeation problem. GHK-Cu is hydrophilic and charged, and the stratum corneum is neither. In an in vitro study across two skin models, the depth and percentage of microneedle penetration correlated with the force applied, which in turn determined the enhancement in permeability. Over nine hours, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated microneedle-treated human skin, while almost no peptide and almost no copper permeated intact human skin ^[10].

That negative result is the most practically important finding in the topical literature, and it is rarely quoted alongside the matrix-synthesis results it would qualify. A concentration that stimulates collagen synthesis at 10⁻⁹ M in a dish ^[1] is only relevant if the molecule reaches a comparable concentration where fibroblasts are, and across intact skin it does not.

The formulation literature since then has addressed the same problem with liposomal encapsulation. A 2025 review of the measurement methods concluded that transport of liposome-encapsulated GHK-Cu across the skin barrier has received little attention and that the analytical methods for assessing it remain to be developed ^[13].

The review literature. A substantial fraction of the secondary literature on this compound — reviews of tissue remodelling, of oxidative stress, and of the gene data — comes from a small number of authors, principally Loren Pickart, who first described the tripeptide's biological activity ^{[4, 6, 11, 12]}. Those reviews are the usual source of the broad claims made for GHK-Cu in popular writing. They are reviews: they summarise primary work, most of it in vitro, and they are cited here as reviews rather than as evidence of effect.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

GHK-Cu vs Related Compounds

Composition and mechanism only; no comparison of effect is made between these compounds.

Molecular class

GHK-Cu — a copper(II) coordination complex of a three-residue peptide. AHK-Cu — the same idea with alanine in place of glycine at position 1. KPV — a three-residue peptide with no metal component, derived from a hormone. BPC-157 and TB-500 — longer peptides studied in tissue-repair models with entirely different proposed mechanisms.

What is bound

GHK-Cu — copper(II), at a conditional dissociation constant of 7.0 × 10⁻¹⁴ M at pH 7.4 ^[5]. TB-500 and thymosin β4 — monomeric actin. KPV — no characterised binding partner. BPC-157 — none identified.

Is the metal the active part?

An open question rather than a settled one. Copper-free GHK reproduced several of the complex's reported effects in keratinocyte and skin-equivalent models ^[8], and free copper ions alone reproduced its effect on TGF-β1 secretion in dermal fibroblasts ^[9]. The literature contains both results and does not reconcile them.

Evidence shape

GHK-Cu — strong coordination chemistry, a long in vitro matrix literature, two animal models, no published trial. BPC-157 — broad rodent literature, no published trial. TB-500 and thymosin β4 — completed phase 3 trials of the full-length protein. Approval status: none of these is an approved medicine in the United States, and approval is specific to a compound and an indication.

Chemical & Molecular Characteristics

The peptide and the complex are separate register entries, and the difference is the copper.

The free tripeptide. Glycyl-L-histidyl-L-lysine, sequence GHK, three standard L-amino acids, no modification. PubChem CID 73587, CAS 49557-75-7, UNII 39TG2H631E, molecular formula C14H24N6O4, average mass 340.4 g/mol. Its INN is prezatide.

The copper complex. PubChem CID 71587328, CAS 89030-95-5, UNII 6BJQ43T1I9. The catalog record behind this page carries the neutral formula C14H24CuN6O4 at 403.9 g/mol, which is the figure in the specification table above.

Why published masses for the complex disagree, and why it does not matter much. PubChem holds several entries for this coordination chemistry: the cation C14H23CuN6O4+ at 402.9 g/mol, an anionic form C14H21CuN6O4⁻ at 400.9 g/mol, and a bis-ligand complex C28H46CuN12O8 at 742.3 g/mol. These describe protonation states and stoichiometries of one system rather than different materials. For a plain peptide a two-dalton discrepancy between listings would be a red flag; for a metal complex written in different conventions it is not. The figures that do carry information for this compound are the copper content and the ligand-to-metal ratio, and those belong on a certificate of analysis rather than on a catalog page.

The binding site. The N-terminal amino group, the position-2 histidine imidazole nitrogen and the deprotonated amide nitrogen between them form the square-planar copper(II) site. This is the same motif that gives human serum albumin its N-terminal copper site through its DAHK sequence, which is why the two were measured side by side in the calorimetry work and why their affinities came out within a factor of three of each other ^[5].

Appearance. The copper complex is coloured — blue to blue-violet — where the free peptide is white. That is a property of the copper(II) d-orbital transitions and is the crudest possible check that a lot is the complex rather than the free peptide; it is not a purity test and no colour observation substitutes for an analytical record.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. 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 letters; 1988. PMID 3169264 doi:10.1016/0014-5793(88)80509-x
2. Wegrowski Y, Maquart FX, Borel JP. Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ Life sciences; 1992. PMID 1522753 doi:10.1016/0024-3205(92)90504-i
3. 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 The Journal of clinical investigation; 1993. PMID 8227353 doi:10.1172/JCI116842
4. Pickart L. The human tri-peptide GHK and tissue remodeling Journal of biomaterials science. Polymer edition; 2008. PMID 18644225 doi:10.1163/156856208784909435
5. Trapaidze A, Hureau C, Bal W, et al.. Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry; 2012. PMID 21898044 doi:10.1007/s00775-011-0824-5
6. Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health Oxidative medicine and cellular longevity; 2012. PMID 22666519 doi:10.1155/2012/324832
7. 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 medicine; 2012. PMID 22937864 doi:10.1186/gm367
8. Choi HR, Kang YA, Ryoo SJ, et al.. Stem cell recovering effect of copper-free GHK in skin Journal of peptide science : an official publication of the European Peptide Society; 2012. PMID 23019153 doi:10.1002/psc.2455
9. Gruchlik A, Chodurek E, Dzierzewicz Z. Effect of GLY-HIS-LYS and its copper complex on TGF-β secretion in normal human dermal fibroblasts Acta poloniae pharmaceutica; 2014. PMID 25745767
10. Li H, Low YS, Chong HP, et al.. Microneedle-Mediated Delivery of Copper Peptide Through Skin Pharmaceutical research; 2015. PMID 25690343 doi:10.1007/s11095-015-1652-z
11. Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration BioMed research international; 2015. PMID 26236730 doi:10.1155/2015/648108
12. Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data International journal of molecular sciences; 2018. PMID 29986520 doi:10.3390/ijms19071987
13. Ogórek K, Nowak K, Wadych E, et al.. Are We Ready to Measure Skin Permeation of Modern Antiaging GHK-Cu Tripeptide Encapsulated in Liposomes? Molecules (Basel, Switzerland); 2025. PMID 39795193 doi:10.3390/molecules30010136
14. Mao S, Huang J, Li J, et al.. Exploring the beneficial effects of GHK-Cu on an experimental model of colitis and the underlying mechanisms Frontiers in pharmacology; 2025. PMID 40672369 doi:10.3389/fphar.2025.1551843
15. Topical GHK-Cu Gel for Acute Skin Wound Healing 2026. NCT07437586

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: GHK-Cu specifications and lot documentation