Regulated as cosmetic ingredients

GHK-Cu

Last reviewed 2026-08-05

Reviewed by HelixEvoLabs Research Team

Technical and cosmetic-regulatory reference for GHK-Cu as a manufactured cosmetic ingredient.

Identity and nomenclature

INN: Not verified
INCI name: Copper Tripeptide-1
Synonyms: Copper Tripeptide-1, prezatide copper, glycyl-L-histidyl-L-lysine copper(II), Cu(II)GHK
Development codes: Not verified

Mechanism

GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine. The registered cosmetic ingredient is a 1:1 peptide-to-copper complex in which the peptide acts as a dianionic tridentate nitrogen donor.

The FDA substance registry records the ingredient as comprising exactly two moieties in a 1:1 molar ratio, the tripeptide and the cupric cation. The CAS systematic index name identifies the donor atoms explicitly as the glycyl alpha-amino nitrogen, the deprotonated glycyl-histidyl peptide amide nitrogen, and the histidyl imidazole nitrogen. The lysine epsilon-amino group is not a donor in this species.

X-ray and solution structural work reports that the complex is dimeric in the solid state but monomeric in solution, with three equatorial nitrogen donors and a labile fourth equatorial site occupied in the solid state by a carboxylate oxygen. Potentiometric work reports that the lysine epsilon-amino group participates in coordination only at alkaline pH, being protonated at physiological pH.

Reported affinity depends entirely on how it is defined. An isothermal titration calorimetry study reports a conditional dissociation constant at pH 7.4 of 7.0 plus or minus 1.0 times ten to the minus fourteen molar, equivalent to a conditional log K of approximately 13.15. A widely repeated overall formation constant of log K 16.44 appears in a review that states neither ionic strength nor temperature nor the species it refers to. These are different quantities and the gap between them is the proton-competition term, so the overall value should not be quoted as the affinity at physiological or skin pH.

Ligand exchange is reported to be rapid, in contrast to the slow exchange of the related DAHK peptide, and an equilibrium dialysis study reports that in the presence of albumin approximately 42 per cent of copper is associated with the peptide at equimolar concentrations, falling to approximately 6 per cent at physiological concentrations.

Analytical data sheet

GHK-Cu

Identity

Molecular formula: C14H22N6O4·Cu
Molecular weight: 401.91 g/mol
CAS number: 89030-95-5
UNII: 6BJQ43T1I9
Chemical name: Copper, (glycyl-κN-L-histidyl-κN,κN3-L-lysinato(2-))-
Appearance: Dark blue-purple crystals; dark purple-blue octahedral crystals on recrystallisation. Blue-violet in aqueous solution

Primary structure

GHK

3 residues

Modifications

Copper(II) coordination complex in 1:1 peptide-to-metal ratio, recorded at moiety level in the FDA substance registry. The peptide is dianionic, deprotonated at the lysine alpha-carboxylate and at the glycyl-histidyl amide nitrogen, giving a neutral complex.
The free tripeptide is separately registered as prezatide, CAS 49557-75-7, UNII 39TG2H631E, molecular formula C14H24N6O4, molecular weight 340.38.
A 2:1 peptide-to-copper species is separately registered as bisprezatide copper, CAS 130120-56-8, and an acetate form as prezatide copper acetate, CAS 130120-57-9, INCI Bis(Tripeptide-1) Copper Acetate. These are distinct substances and should not be conflated with the 1:1 complex.
The registry number 89030-95-9, which circulates widely, is not a valid CAS Registry Number: the check-digit algorithm admits only 5 for that sequence, and the number returns no result in the FDA substance registry.
The EU cosmetic inventory carries eight distinct ingredients whose names contain both copper and tripeptide-1, and they are not interchangeable. Two of them post their own registry numbers: BIS(TRIPEPTIDE-1) COPPER ACETATE at 130120-57-9 and COPPER TRIPEPTIDE-1 PALMITAMIDE at 2133832-31-0. Neither is this compound. An incoming specification naming any of the eight should be matched against the intended ingredient rather than assumed to mean the copper tripeptide-1 complex.

Solubility

Water: Soluble. The published preparation dissolves the complex at approximately 100 mg/mL scale in aqueous copper(II) acetate; the free tripeptide is handled at 50 mg/mL in distilled water. Both figures are working concentrations rather than saturation limits
Ethanol: Functions as an anti-solvent. Ethanol is added to aqueous solution specifically to reach a cloud point and precipitate the complex, so high-ethanol systems are expected to drop it out of solution

Storage

No storage conditions established from a primary source.

Stability

The free tripeptide is reported stable in water and in pH 4.5 to 7.4 buffers for at least two weeks at 60 degrees Celsius, with first-order degradation kinetics under stress.
Degradation proceeds by hydrolytic cleavage under basic and oxidative conditions, with minimal degradation under acidic stress.
Copper redox activity is attenuated but not abolished on complexation. One review states that redox activity is silenced; a later study reports that the complex does produce reactive oxygen species, at significantly lower levels than free copper(II). Electrochemical work reports reduction to copper(I) at approximately minus 0.62 volts versus a silver chloride reference with subsequent release of the copper ion, which is consistent with the complex being redox-accessible rather than inert.
Ligand exchange is rapid and the fourth coordination site is labile, so the complex is expected to lose copper to stronger competing chelators.
In near-neutral aqueous systems, excess copper(II) precipitates as the hydroxide and is removed by centrifugation during manufacture.

Analytical methods

Method	Purpose	Specification
UV-Visible spectrophotometry	Complex-formation confirmation and speciation. The copper(II) d-d absorption band is reported at 606 nm by two independent groups, and shifts in this band track changes in coordination number	Not verified
ICP-MS	Element-specific copper quantification	Not verified
CE-ICP-MS/MS	Speciation-preserving copper determination, monitoring the copper-63 signal to distinguish encapsulated from free complex without prior separation	Not verified
RP-HPLC with UV detection	Quantification in cosmetic formulation. Published conditions are partial: ODS C18 column, 0.2 per cent trifluoroacetic acid, detection at 220 nm. Column dimensions, gradient, flow rate and validation data are not published	Not verified
EPR spectroscopy	Confirmation of the nitrogen donor set. Reported parallel hyperfine coupling 19.5 millitesla and g-parallel 2.21, with seven-line nitrogen superhyperfine splitting indicating three coordinated nitrogen atoms	Not verified

Impurities and degradation products

Commercial free tripeptide is reported to be approximately 95 per cent pure. The principal named process impurity is poorly water-soluble material described as tripeptide not completely deblocked of protecting groups during the final synthetic step.
Mass spectrometry has identified three degradation products under stress, one of which is histidine, a constituent amino acid. The other two are not named in the published record.
Excess copper(II) hydroxide is a documented process-related insoluble impurity removed by centrifugation.

Handling

No REACH registration or harmonised classification was located for this substance, which is consistent with cosmetic-only use. Occupational controls are therefore set by the receiving facility under its own assessment rather than by a harmonised hazard classification.

Ingredient safety assessment

Cosmetic Ingredient Review Expert Panel

The panel concluded that the assessed ingredients, which include Copper Tripeptide-1 and Bis(Tripeptide-1) Copper Acetate, are safe in the present practices of use and concentration in cosmetics described in the assessment.

The assessment records reported use concentrations for the group between 0.0000001 and 0.002 per cent, with an industry submission indicating customary peptide use below 10 parts per million

Cosmetic Ingredient Review Final Report on Tripeptide-1, Hexapeptide-12 and related ingredients · verified 2026-07-30

Reported research findings

in vitro
The study reported that stimulation of collagen synthesis began between 10 to the minus twelve and 10 to the minus eleven molar and was maximal at 10 to the minus nine molar, independent of any change in cell number.
Fibroblast culture, collagen synthesis measurement
Limitations: In vitro only. The published abstract does not state whether copper alone or peptide alone were run as separate control arms, which is what would distinguish a peptide-specific effect from copper delivery. An author of this study is affiliated with a commercial copper-peptide company.
animal
The study reported increased wound tissue production and glycosaminoglycan synthesis, enhanced accumulation of chondroitin sulfate and dermatan sulfate, increased decorin messenger RNA and decreased biglycan messenger RNA.
Rat wound-chamber model with companion rat dermal fibroblast cultures, Northern blot analysis
Limitations: Animal and cell-culture model. Findings in a rat wound chamber are not transferable to cosmetic use on intact human skin.
human · n=13
The study reported no statistically significant difference between groups for resolution of erythema, and no difference between groups in wrinkles or overall skin quality on objective evaluation. A difference in patient-reported improvement in overall skin quality reached significance at p equals 0.04.
Randomised study in patients following carbon dioxide laser resurfacing, with erythema assessed by computer analysis and by blinded evaluators, plus a validated patient questionnaire at 12 weeks
Limitations: Thirteen participants completed. The only endpoint reaching significance was patient self-report; all objective endpoints were null. This is the clearest randomised peer-reviewed human study located for this ingredient.
in vitro
The study measured copper distribution across skin layers and in receptor fluid following application of an aqueous copper-peptide solution.
In vitro percutaneous absorption using flow-through diffusion cells on isolated stratum corneum, heat-separated epidermis and dermatomed human skin, with ICP-MS quantification over 48 hours
Limitations: In vitro human skin model. The measurement is element-specific for copper and does not by itself establish that the intact complex crossed the barrier.
review
The analysis reported that of 13,424 human genes assayed, exposure was associated with at least a 50 per cent expression change in 4,192, approximately 31 per cent, of which 59 per cent increased and 41 per cent were suppressed.
Computational reanalysis of a public transcriptional perturbation database derived from cultured cell lines
Limitations: This is a database query against pre-existing transcriptional data generated in cultured cell lines. It is not a skin study, not a human study, and not an experiment performed on skin tissue. The authors are affiliated with a commercial copper-peptide company while declaring no conflict of interest.

Regulatory status by jurisdiction

United States
Cosmetic Ingredient Review / FDA
Cosmetic ingredient
Used as a cosmetic ingredient. The Cosmetic Ingredient Review expert panel assessed Copper Tripeptide-1 and concluded that the ingredients reviewed are safe in the present practices of use and concentration described in the assessment.
Safety Assessment of Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in CosmeticsVerified 2026-07-30
European Union
European Commission
Cosmetic ingredient
Listed in the Commission cosmetic ingredient database as COPPER TRIPEPTIDE-1 with the reported function skin conditioning. It appears in none of the annexes to Regulation (EC) No 1223/2009, so no prohibition, restriction, positive listing or maximum concentration applies to it, and no Scientific Committee on Consumer Safety opinion covers it.
CosIng ingredient record, COPPER TRIPEPTIDE-1Verified 2026-07-31
United Kingdom
Office for Product Safety and Standards
Cosmetic ingredient
Lawful as a cosmetic ingredient in Great Britain. The ingredient appears in none of the annexes to assimilated Regulation (EC) No 1223/2009, which is enforced under the Cosmetic Products Enforcement Regulations 2013. The word tripeptide does not occur anywhere in the Great Britain annexes.
Regulation (EC) No 1223/2009, as assimilated law applying in Great BritainVerified 2026-07-31

Regulatory classification by jurisdiction, with source document and verification date
Jurisdiction	Classification	Summary	Source	Verified
United StatesCosmetic Ingredient Review / FDA	Cosmetic ingredient	Used as a cosmetic ingredient. The Cosmetic Ingredient Review expert panel assessed Copper Tripeptide-1 and concluded that the ingredients reviewed are safe in the present practices of use and concentration described in the assessment. Reported function is skin-conditioning agent; the panel assessment records typical use concentrations below 10 parts per million	Safety Assessment of Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics	2026-07-30
European UnionEuropean Commission	Cosmetic ingredient	Listed in the Commission cosmetic ingredient database as COPPER TRIPEPTIDE-1 with the reported function skin conditioning. It appears in none of the annexes to Regulation (EC) No 1223/2009, so no prohibition, restriction, positive listing or maximum concentration applies to it, and no Scientific Committee on Consumer Safety opinion covers it. Absence from the annexes is not an approval. Compliance rests on the Article 3 general safety obligation, an Article 10 safety report prepared by a qualified assessor, a responsible person established in the territory, notification to the competent authority, and Article 19 labelling using the common ingredient nomenclature Copper is not prohibited as a class. Annex II lists individually named copper substances only, several restricted to hair dye products, and non-nano metallic copper is a permitted Annex IV colorant, reference 132, colour index 77400, without conditions Nanoparticulate and colloidal metallic copper are prohibited in the European Union under Annex II reference 1726, added by Commission Regulation (EU) 2024/858. This bites only on nano or colloidal copper raw material, not on this complex	CosIng ingredient record, COPPER TRIPEPTIDE-1	2026-07-31
United KingdomOffice for Product Safety and Standards	Cosmetic ingredient	Lawful as a cosmetic ingredient in Great Britain. The ingredient appears in none of the annexes to assimilated Regulation (EC) No 1223/2009, which is enforced under the Cosmetic Products Enforcement Regulations 2013. The word tripeptide does not occur anywhere in the Great Britain annexes. Absence from the annexes is not an approval. Compliance rests on the Article 3 general safety obligation, an Article 10 safety report prepared by a qualified assessor, a responsible person established in the territory, notification to the competent authority, and Article 19 labelling using the common ingredient nomenclature Copper is not prohibited as a class. Annex II lists individually named copper substances only, several restricted to hair dye products, and non-nano metallic copper is a permitted Annex IV colorant, reference 132, colour index 77400, without conditions Great Britain has NOT adopted the European Union prohibition on nano and colloidal copper, and Annex II reference numbers have diverged between the two jurisdictions, so entries must not be cross-cited by number Northern Ireland follows the live European Union Regulation rather than the Great Britain consolidation, including the nano copper prohibition, and requires a responsible person established in Northern Ireland or the European Union	Regulation (EC) No 1223/2009, as assimilated law applying in Great Britain	2026-07-31

Supply classification and permitted use

GHK-Cu is regulated as a cosmetic ingredient rather than as a medicinal product. Material is supplied to businesses as a cosmetic raw material for formulation and manufacturing purposes. No medicinal claims are made for it.

A cosmetic ingredient safety assessment is an assessment of safety in use at stated concentrations. It is not a marketing authorisation and it is not a finding of efficacy.
Responsibility for the safety assessment of a finished cosmetic product rests with the responsible person placing that product on the market.

How supply classifications work · Documented safety signals

References

[1]LegislationConsolidated Regulation (EC) No 1223/2009 on cosmetic products, consolidated text of 1 May 2026 — EUR-Lex, 2026 · accessed 2026-07-31
[2]LegislationRegulation (EC) No 1223/2009 on cosmetic products, as assimilated law applying in Great Britain — UK Statute Law Database, 2026 · accessed 2026-07-31
[3]LegislationThe Cosmetic Products Enforcement Regulations 2013 (S.I. 2013/1478) — UK Statute Law Database, 2013 · accessed 2026-07-31
[4]RegulatorRegulation 1223/2009 and the Cosmetic Products Enforcement Regulations 2013: Great Britain — Office for Product Safety and Standards, 2026 · accessed 2026-07-31
[5]NomenclatureCosIng ingredient record, COPPER TRIPEPTIDE-1 — European Commission, 2026 · accessed 2026-08-05
[6]Safety assessmentSafety Assessment of Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics — Final Report — Cosmetic Ingredient Review, 2014 · accessed 2026-07-30
[7]Safety assessmentJohnson W Jr, Bergfeld WF, Belsito DV, et al.. Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics — SAGE Publishing, International Journal of Toxicology, 2018 · doi:10.1177/1091581818807863 · accessed 2026-07-30
[8]NomenclaturePREZATIDE COPPER — Global Substance Registration System record, UNII 6BJQ43T1I9 — US Food and Drug Administration, 2026 · accessed 2026-07-30
[9]NomenclaturePREZATIDE — Global Substance Registration System record, UNII 39TG2H631E — US Food and Drug Administration, 2026 · accessed 2026-07-30
[10]Peer-reviewedHureau 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 — Wiley, Chemistry - A European Journal, 2011 · doi:10.1002/chem.201100751 · PMID 21780203 · accessed 2026-07-30
[11]Peer-reviewedTrapaidze A, Hureau C, Bal W, Winterhalter M, Faller P. Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry with the weaker competitor glycine — Springer, Journal of Biological Inorganic Chemistry, 2012 · doi:10.1007/s00775-011-0824-5 · PMID 21898044 · accessed 2026-07-30
[12]Peer-reviewedLau SJ, Sarkar B. The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma — Portland Press, Biochemical Journal, 1981 · PMID 7340824 · accessed 2026-07-30
[13]Peer-reviewedConato C, Gavioli R, Guerrini R, et al.. Copper complexes of glycyl-histidyl-lysine and two of its synthetic analogues: chemical behaviour and biological activity — Elsevier, Biochimica et Biophysica Acta, 2001 · doi:10.1016/s0304-4165(01)00127-1 · PMID 11325542 · accessed 2026-07-30
[14]Peer-reviewedBadenhorst 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 — Taylor and Francis, Pharmaceutical Development and Technology, 2016 · doi:10.3109/10837450.2014.979944 · PMID 25384620 · accessed 2026-07-30
[15]Peer-reviewedUfnalska I, Drew SC, Zhukov I, et al.. Intermediate Cu(II)-thiolate species in the reduction of Cu(II)GHK by glutathione: a handy chelate for biological Cu(II) reduction — American Chemical Society, Inorganic Chemistry, 2021 · doi:10.1021/acs.inorgchem.1c02669 · accessed 2026-07-30
[16]Peer-reviewedBossak-Ahmad K, Wiśniewska MD, Bal W, Drew SC, Frączyk T. Ternary Cu(II) complex with GHK peptide and cis-urocanic acid as a potential physiologically functional copper chelate — MDPI, International Journal of Molecular Sciences, 2020 · doi:10.3390/ijms21176190 · accessed 2026-07-30
[17]Peer-reviewedLaussac JP, Haran R, Sarkar B. N.m.r. and e.p.r. investigation of the interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma — Portland Press, Biochemical Journal, 1983 · PMID 6318731 · accessed 2026-07-30
[18]Peer-reviewedGlycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro — Oxford University Press, Metallomics, 2024 · doi:10.1093/mtomcs/mfae019 · accessed 2026-07-30
[19]Peer-reviewedHostynek 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 — Springer, Inflammation Research, 2010 · doi:10.1007/s00011-010-0214-4 · accessed 2026-07-30
[20]Peer-reviewedZajda J, Wadych E, Ogórek K, Drozd M, Matczuk M. Novel applications of CE-ICP-MS/MS: monitoring of antiaging GHK-Cu cosmetic component encapsulation in liposomes — Wiley, Electrophoresis, 2024 · doi:10.1002/elps.202400047 · PMID 39451062 · accessed 2026-07-30
[21]Peer-reviewedDymek M, Olechowska K, Hąc-Wydro K, Sikora E. Liposomes as carriers of GHK-Cu tripeptide for cosmetic application — MDPI, Pharmaceutics, 2023 · doi:10.3390/pharmaceutics15102485 · accessed 2026-07-30
[22]Peer-reviewedMaquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ — Elsevier, FEBS Letters, 1988 · doi:10.1016/0014-5793(88)80509-X · PMID 3169264 · accessed 2026-07-30
[23]Peer-reviewedSiméon A, Wegrowski Y, Bontemps Y, Maquart FX. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+) — Elsevier, Journal of Investigative Dermatology, 2000 · doi:10.1046/j.1523-1747.2000.00166.x · PMID 11121126 · accessed 2026-07-30
[24]Peer-reviewedMiller TR, Wagner JD, Baack BR, Eisbach KJ. Effects of topical copper tripeptide complex on CO2 laser-resurfaced skin — American Medical Association, Archives of Facial Plastic Surgery, 2006 · doi:10.1001/archfaci.8.4.252 · PMID 16847171 · accessed 2026-07-30
[25]Peer-reviewedPickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data — MDPI, International Journal of Molecular Sciences, 2018 · doi:10.3390/ijms19071987 · accessed 2026-07-30

Scope of this reference

This knowledge base is scientific and regulatory reference material for businesses. It is not medical advice, not a recommendation, and not product promotion. Regulatory classification differs by jurisdiction, by form and by route of administration, and a statement recorded for one territory does not describe the position in another.

HelixEVO does not supply medicinal products for human administration. Material is supplied to businesses for research and manufacturing purposes only. Where a compound holds no marketing authorisation, human administration outside an authorised clinical trial is not a lawful supply route.

Every regulatory and analytical statement carries its source and the date it was last verified. Where a value could not be established from a primary source it is recorded as unverified rather than estimated.