GHK-Cu (Prezatide Copper)

Six database records answer to one name

A PubChem name search for GHK-Cu returns six compound identifiers. CID 73587 is the metal-free tripeptide, C14H24N6O4 at 340.38 g/mol, CAS 49557-75-7. CID 71587328 is prezatide copper, C14H23CuN6O4+ at 402.92, CAS 89030-95-5. CID 165429100 is a neutral 1:1 complex, C14H22CuN6O4 at 401.91, with no registry number attached. CID 139035031 is a 1:1 anion, C14H21CuN6O4 minus, at 400.90. CID 9831891 is bis-prezatide copper, C28H46CuN12O8 at 742.3, CAS 130120-56-8, and CID 133697840 is a related bis form at 744.3 carrying CAS 300801-03-0, a registry number that CID 9831891 also lists among its own synonyms.

The FDA record does not agree with the PubChem record that carries its own identifier. Global Substance Registration System UNII 6BJQ43T1I9, name PREZATIDE COPPER, status approved, gives the formula as C14H22N6O4.Cu with a molecular weight of 401.9085 and CAS 89030-95-5. PubChem CID 71587328 carries that same CAS number and that same UNII and reports 402.92 for a cationic form one hydrogen heavier. The gap is about one dalton. It is small, it is the sort of thing an automated structure normalisation produces, and it means the two authoritative records for the same registered substance state different masses.

Synonym lists compound the problem rather than resolving it. The metal-free peptide record, CID 73587, lists GHK-Cu, Copper Peptide and Tripeptide-1 among its synonyms alongside Prezatide, so a record for a molecule containing no copper is indexed under the name of its copper complex. The same list also carries a cedarwood-oil trade designation, which is a useful reminder that these synonym sets are machine-assembled and not curated. Across the six records listed above the quoted masses span 340.38 to 744.3 g/mol, a factor of 2.19, so any molar figure quoted without naming the stoichiometry, charge state and salt form is ambiguous over that range.

What the rodent and rabbit wound models measured

Maquart and colleagues, publishing in the Journal of Clinical Investigation in 1993, implanted stainless steel wire mesh cylinders subcutaneously in rats and injected either saline or a range of GHK-Cu concentrations into the chamber. Dry weight, DNA, total protein, collagen and glycosaminoglycan content all rose with concentration. Stimulation of collagen synthesis was twice that of non-collagen proteins. Type I and type III collagen mRNAs increased while TGF-beta mRNAs did not, and a control tripeptide, L-glutamyl-L-histidyl-L-proline, produced no significant effect. Group sizes are not stated in the retrieved report.

Simeon and colleagues used the same chamber model in Sprague-Dawley rats in 1999, with serial 2 mg injections. Pro-MMP-2 and activated MMP-2 rose during the later stages of healing, at day 18 and/or day 22, MMP-9 expression persisted in treated chambers to day 22, and interstitial collagenase activity was unchanged. Their 2000 follow-up reported that the MMP-2 increase was reproduced by copper ions alone and not by the tripeptide alone (PMID 11045606).

Topical work is more recent and better quantified. Canapp and colleagues in 2003 created 6 mm full-thickness wounds inside ischaemic bipedicle skin flaps on 24 adult male Sprague-Dawley rats and traced margins daily for 13 days; the decrease from initial wound area at day 13 was 64.5% with the copper complex, 45.6% with vehicle and 28.2% untreated, and treated biopsies carried lower TNF-alpha, MMP-2 and MMP-9. Cangul and colleagues in 2006 randomised 18 New Zealand rabbits across copper complex, zinc oxide and no treatment, applying daily for 21 days, and reported smaller mean unhealed area than untreated control at days 7, 14 and 21.

What happened when it was tested in people

Two trials from the 1990s point in opposite directions. Mulder and colleagues reported a multicentre, randomised, evaluator-blinded, placebo-controlled study of a copper-peptide gel in diabetic neuropathic ulcers in 1994: median area percentage closure of plantar ulcers was 98.5% against 60.8% for vehicle, the difference was larger in ulcers above 100 mm-squared at entry, at 89.2% against minus 10.3%, and ulcer infection occurred in 7% of treated plantar ulcers against 34% on vehicle. The report does not state enrolment numbers in the retrievable record.

Bishop and colleagues had already published the opposite result in the Journal of Vascular Surgery in 1992. Eighty-six evaluable patients with venous stasis ulcers completed a prospective randomised evaluator-blinded comparison of 1% silver sulfadiazine cream, a 0.4% tripeptide-copper complex cream and an inert vehicle. Silver sulfadiazine reduced ulcer size relative to the other two arms. Between the copper complex and the placebo there was no difference. That is a null result in venous stasis ulcers, published in a major surgical journal.

The decisive dataset was never published at all. Contemporaneous trade and newspaper reporting records that in October 1994 the developer completed a 511-patient trial, across diabetic ulcers and other wound types, in which the gel failed to outperform control, although it was recorded as safe, and that this ended the effort to register the compound as a drug. A Seattle Times report dated 7 February 1996 describes the eventual FDA action as clearance of a wound-care product with the wound-healing drug claim expressly prohibited. PubMed returns no publication corresponding to a 511-patient trial of this compound. The largest human dataset that exists on GHK-Cu is a negative one, and it exists only as journalism.

Later human work is small and mostly cosmetic. Miller and colleagues in 2006 randomised patients undergoing carbon dioxide laser resurfacing to post-treatment regimens with or without GHK-Cu; thirteen completed, blinded evaluators and computer analysis found no significant difference in erythema resolution, wrinkles or skin quality, and the only significant difference was on a patient questionnaire, at P equal to 0.04. Lee and colleagues in 2016 treated 45 men with pattern hair loss using a complex of 5-aminolevulinic acid and GHK at two strengths or placebo for six months; hair-count change was 52.6 at the higher strength, 71.5 at the lower and 9.6 on placebo, and only the lower strength separated from placebo. Neither trial isolates GHK-Cu.

The gene-expression claim and its actual source

Campbell and colleagues profiled gene expression across eight regions from each of eight lungs from smokers with chronic obstructive pulmonary disease, 64 samples in total, quantifying regional emphysema severity by mean linear intercept from micro-CT. They identified 127 genes whose expression tracked emphysema severity, then queried the Broad Institute Connectivity Map for compounds whose expression signature ran opposite to that pattern. GHK came back as a hit. Treating human fibroblasts with GHK reproduced TGF-beta-associated expression patterns, organised the actin cytoskeleton and raised integrin beta-1. The paper appeared in Genome Medicine in 2012.

Campbell 2012 is the primary experimental work underneath the gene-regulation literature on this compound. A Connectivity Map hit is a computational nomination generated by matching transcriptional signatures across a reference library; it identifies a candidate for testing, and Campbell's group then did test one, in fibroblasts, on a narrow readout. The step from 127 emphysema-associated genes in 64 lung samples to the figure of 4,000 genes that circulates is not documented in any primary paper. Reviews by the compound's original discoverer state it directly, without a citation attached to the sentence.

Scale matters here in a specific way. The 127-gene signature is a measurement made on human tissue with a defined severity metric. The 4,000-gene figure is a count of records returned by a similarity query against a compound-perturbation database, which is a different kind of object entirely and is not an experimental result about any tissue. Both appear in the same secondary paragraphs, usually without the distinction being drawn.

Copper binding, skin penetration, and the systemic question

Trapaidze and colleagues used isothermal titration calorimetry with glycine as a weaker competing ligand and reported a conditional dissociation constant of 7.0 plus or minus 1.0 times ten to the minus fourteen molar for GHK at pH 7.4, against 2.6 plus or minus 0.4 times ten to the minus fourteen for the albumin-derived DAHK motif, with predominantly 1:1 stoichiometry. Conato and colleagues had earlier characterised the equilibria by potentiometry, calorimetry and spectroscopy, and concluded that complex formation is driven by the N-terminal glycine while the histidine residue does not appear to play a specific role.

Penetration has been measured on human tissue but not in a living person. Hostynek and colleagues applied the compound as the cuprate diacetate at 0.68% aqueous copper to isolated stratum corneum, heat-separated epidermis and dermatomed human skin in flow-through diffusion cells, and reported a permeability coefficient through dermatomed skin of 2.43 plus or minus 0.51 times ten to the minus four centimetres per hour, with 136.2 plus or minus 17.5 micrograms per square centimetre of copper crossing and 82 plus or minus 8.1 retained as a depot over 48 hours. Badenhorst and colleagues measured log D between minus 2.38 and minus 2.49 across pH 4.5 to 7.4, confirming a strongly hydrophilic molecule, and identified three degradation products under stress, one of them free histidine.

Systemic behaviour is characterised in one species only. Endo and colleagues developed an HPLC assay for rat plasma in 1997 and applied it after a single intravenous dose: GHK was rapidly degraded to the dipeptide His-Lys, which was itself eliminated rapidly. No human pharmacokinetic study of GHK-Cu by any route was located in PubMed. Every figure in circulation describing what happens to injected material in a person is therefore an extrapolation from a rat assay paper whose stated purpose was method development.

The registered record and the 2026 literature

ClinicalTrials.gov returns three studies mentioning this compound. NCT07437586 is a phase 2, randomised, quadruple-masked, vehicle-controlled split-wound study of a topical GHK-Cu gel at 0.1% w/w applied once daily for 14 days in 60 healthy adults; it began on 2 February 2026, is recruiting at a single site and has posted no outcome data. NCT05932732 is a completed 27-participant facial-skin study in which a GHK-Cu-containing serum was one component of a device protocol rather than an isolated variable. NCT07706361 is a two-part, placebo-controlled trial of a transdermal patch device, registered as not yet recruiting with a planned 100 participants and an estimated start of January 2027; it administers no GHK-Cu and proposes only to measure endogenous circulating GHK and GHK-Cu concentrations in healthy adults. No registered trial has reported an outcome.

Preclinical output continues and has widened past dermatology. Wen and colleagues reported in Biogerontology in 2026 that GHK-Cu extended lifespan in Caenorhabditis elegans and shifted mitochondrial dynamics toward fusion, with DAF-16 and SKN-1 pathway activation (PMID 42084774). Mazzola and colleagues posted a bioRxiv preprint in 2026 (doi 10.64898/2026.04.09.717524, posted 13 April 2026) comparing intraperitoneal and intranasal delivery of 15 mg/kg in C57BL/6J mice aged 20 to 21 months: eight weeks of intranasal dosing improved escape latency in both sexes across trials 2 to 4, while five days of intraperitoneal dosing produced only a transient improvement in males, alongside divergent hippocampal transcriptional programmes; that manuscript has not been peer reviewed. Alferova and colleagues, testing the Vogel conflict paradigm in 2025, reported that GHK itself produced no anxiolytic effect, in contrast to proline-containing analogues (PMID 41511598).

Regulatory position has not changed since 1996. Copper tripeptide-1 appears in cosmetic formulations and the FDA substance record for prezatide copper is marked approved in the registration sense, which records an identified substance rather than an authorised medicine. No jurisdiction has approved GHK-Cu as a drug for any indication, and no injectable presentation has been authorised anywhere. Two 2026 reviews in sports-medicine journals, by Mendias and Awan (PMID 41966639) and by Tewari and colleagues (PMID 42578445), place it explicitly within the category of unapproved peptides sold direct to patients and note the scarcity of rigorous human safety data across that category.

What is not known

No completed trial has established a clinical outcome for GHK-Cu, and the largest trial ever run on it is not in the literature at all: the 511-patient study that ended the drug programme in October 1994 exists only in contemporaneous trade and newspaper reporting, so its design, endpoints, effect estimates and adverse-event tables cannot be read by anyone. The two published trials in chronic wounds disagree, one reporting a large difference against vehicle in diabetic neuropathic ulcers and the other none in venous stasis ulcers, and neither has been replicated. Enrolment numbers are absent from the retrievable record for the positive one. Everything downstream of the skin is uncharacterised in humans: no pharmacokinetic study by any route, no bioavailability figure, no tissue distribution, no repeat-exposure data, and no study addressing whether repeatedly delivering a chelated copper load perturbs systemic copper homeostasis. The single administration study in any species, Endo 1997, found the peptide degraded rapidly to a dipeptide after intravenous dosing in rats, and no work has followed it up. The mechanistic literature has an unresolved attribution problem, since Simeon 2000 reported that copper ions alone reproduced the metalloproteinase effect and the tripeptide alone did not. Nothing addresses use in pregnancy, in children, in people with impaired copper handling, or over any period longer than the six months of the hair trial. GHK-Cu is not an approved medicine in any jurisdiction, and no injectable presentation has been authorised anywhere.

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