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Skin & Aesthetic ResearchTissue RepairImmune & Inflammatory ResearchExperimental / endogenous complex

GHK-Cu

Copper(II) complex of glycyl-L-histidyl-L-lysine

GHK-Cu is the copper(II) complex of the endogenous tripeptide glycyl-L-histidyl-L-lysine. Published work spans coordination chemistry, extracellular-matrix regulation, wound models, skin permeation and a limited human wound-care literature; these domains are not interchangeable evidence of general aesthetic benefit.[1]

Reviewed 2026-09-02

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01 / Overview

Quick facts

Somente campos atualmente documentados aparecem neste registro.

class
Copper-binding tripeptide complex
molecule Type
Peptide-metal complex
primary Target
No single validated pharmacological receptor
primary Axis
Copper handling / extracellular-matrix biology
research Status
Experimental / endogenous complex
first Described
1970s–1980s

What is it studied for?

preliminary
Diabetic neuropathic ulcer closure

A multicenter randomized evaluator-blinded study evaluated a topical GHK-Cu gel alongside standardized wound care.

preclinical
Extracellular-matrix regulation

Fibroblast and wound-model studies reported changes in collagen, glycosaminoglycans and matrix metalloproteinases.

mechanistic
Copper coordination and transport

Spectroscopic and albumin-binding studies characterize copper coordination and exchange rather than clinical efficacy.

preclinical
Skin penetration

Model-membrane and ex vivo human-skin experiments studied penetration and retention; they do not establish therapeutic benefit.

02 / Mechanism

Mechanism of action

Fluxo estruturado para navegação. Uma seta indica sequência conceitual, não necessariamente interação direta.

GHK copper coordination
Albumin-associated copper exchange
Cell and matrix context
Fibroblast response
Collagen / glycosaminoglycan synthesis and matrix proteolysis
Tissue-remodeling outcomes

03 / Evidence synthesis

What does the evidence actually show?

As categorias evitam misturar evidência humana, dados pré-clínicos e plausibilidade mecanística. A cobertura desta versão não é uma revisão sistemática.

established

Data not indexed yet.

supported

Data not indexed yet.

preliminary
  • Human evidence is limited and indication-specific.
preclinical
  • Matrix and wound biology have broader cellular and animal support than clinical support.
mechanistic
  • Copper coordination is well characterized, but no single GHK-Cu receptor has been validated.
Unsupported / exaggerated
  • The indexed corpus does not establish systemic anti-aging, broad rejuvenation, hair-regrowth or neurodegenerative-disease treatment claims.
  • Ex vivo skin penetration is not evidence of clinical efficacy.
  • Effects of GHK alone, derivatives or multicomponent cosmetics are not automatically attributable to isolated GHK-Cu.

Published evidence

What does the evidence actually show?

Human
1
Animal
4
In vitro
9
Ex vivo
1
Reviews
0
preliminaryhuman · low

One indexed randomized topical study reported improved closure measures in diabetic neuropathic ulcers under standardized wound care. [6]

  • Older, indication-specific study
  • Does not establish general skin rejuvenation
preclinicalmixed · moderate

Cell-culture and animal-wound studies support context-dependent modulation of collagen, glycosaminoglycans and matrix metalloproteinases. [3][4][5][8][9][10]

mechanisticmechanistic · moderate

Spectroscopic studies establish defined Cu(II) coordination, while later work supports exchange with human serum albumin. [1][2][13]

preclinicalin-vitro · low

GHK reduced metal-associated aggregation and cell death in vitro; relevance to human neurodegenerative disease remains unestablished. [14]

04 / Published protocols

Dosing reported in published human studies

The values reproduce protocols described in published research. They are not recommendations, prescriptions or clinical guidance.

Dosing reported in published human studies
StudyPopulationNRouteDose reportedFrequencyDurationDesignPrimary outcomeReference
G. D. Mulder et al.Patients with diabetic neuropathic plantar ulcers receiving standardized wound careNot reported in the consulted sourceTopicalMetered dose of Lamin gel; amount not reported in the indexed abstractDaily—human-rct · needs-reviewUlcer area closure; Rate of closure; Ulcer infectionOpen

Experimental protocols

Experimental protocols

In vitro concentrations, ex vivo conditions and animal doses are experimental protocols and are not equivalent to human doses.

Experimental protocols
StudyPopulationNRouteDose reportedFrequencyDurationDesignPrimary outcomeReference
J. H. Freedman et al.Spectroscopic solution systemNot reported in the consulted source————in-vitro · verifiedCu(II)-GHK coordination structure across pHOpen
J. P. Laussac et al.NMR and EPR solution systemNot reported in the consulted source————in-vitro · verifiedCu(II) coordination across pHOpen
F. X. Maquart et al.Fibroblast culturesNot reported in the consulted source————in-vitro · needs-reviewCollagen synthesisOpen
Y. Wegrowski et al.Normal human fibroblastsNot reported in the consulted source—Concentration-response experiment; maximal response reported at 10⁻⁹ to 10⁻⁸ M——in-vitro · verifiedGlycosaminoglycan synthesisOpen
F. X. Maquart et al.Experimental rat woundsNot reported in the consulted source————animal · needs-reviewConnective-tissue accumulation in woundsOpen
D. Godet et al.Osteoblastic cellsNot reported in the consulted source————in-vitro · needs-reviewCell spreading, attachment and phenotypeOpen
A. Siméon et al.Experimental woundsNot reported in the consulted source————animal · needs-reviewMatrix metalloproteinase expression and activationOpen
A. Siméon et al.Fibroblast culturesNot reported in the consulted source————in-vitro · needs-reviewMMP-2 expressionOpen
A. Siméon et al.Experimental woundsNot reported in the consulted source————animal · needs-reviewGlycosaminoglycan and proteoglycan expressionOpen
L. Mazurowska et al.Flynn diffusion-cell liposome membrane modelNot reported in the consulted source————in-vitro · verifiedComplex formation and membrane permeabilityOpen
J. J. Hostynek et al.Isolated stratum corneum, epidermis and dermatomed human skinNot reported in the consulted sourceTopical ex vivo0.68% aqueous copper as tripeptide under infinite-dose conditions—48 hoursex-vivo · verifiedCopper permeation and retention by skin layerOpen
K. Bossak-Ahmad et al.Human serum albumin coordination systemNot reported in the consulted source————in-vitro · verifiedStructure and conditional binding constants of ternary Cu(GHK)-albumin complexesOpen
J. H. Min et al.Central-nervous-system cell and protein-aggregation modelsNot reported in the consulted source————in-vitro · needs-reviewMetal-induced protein aggregation; Cell deathOpen
J. Hu et al.CuSO4- or LPS-induced inflammatory larval modelsNot reported in the consulted source————animal · needs-reviewInflammatory-model endpointsOpen

05 / Pharmacokinetics

Pharmacokinetics

Systemic human pharmacokinetics
Not established in the indexed corpus
Topical disposition
Skin retention and permeation were studied ex vivo under experimental conditions
Albumin interaction
Ternary Cu(GHK)-albumin complexes have been characterized in solution

06 / Safety

Safety & Adverse Events

Reported findings

  • The indexed diabetic-ulcer study evaluated topical treatment and reported fewer ulcer infections in the immediate-treatment group.

Pharmacological concerns

  • Safety is formulation-, route-, concentration- and population-dependent.
  • Copper handling and redox biology make extrapolation across experimental systems inappropriate.

Unknowns

  • Long-term systemic exposure and uncommon harms are not adequately characterized.
  • Absence of a reported event in small or preclinical studies is not evidence of safety.

07 / Source literature

Studies

15 indexed
in-vitro1982

Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution

Biochemistry · J. H. Freedman et al.

→
in-vitro1983

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

Biochemical Journal · J. P. Laussac et al.

→
in-vitro1988

Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+

FEBS Letters · F. X. Maquart et al.

→
in-vitro1992

Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+

Life Sciences · Y. Wegrowski et al.

→
animal1993

In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds

Journal of Clinical Investigation · F. X. Maquart et al.

→
human-rct1994

Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper

Wound Repair and Regeneration · G. D. Mulder et al.

→
in-vitro1995

Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype

Cellular and Molecular Biology · D. Godet et al.

→
animal1999

Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+

Journal of Investigative Dermatology · A. Siméon et al.

→
in-vitro2000

The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures

Life Sciences · A. Siméon et al.

→
animal2000

Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+)

Journal of Investigative Dermatology · A. Siméon et al.

→
in-vitro2007

ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum

Talanta · L. Mazurowska et al.

→
ex-vivo2010

Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy

Inflammation Research · J. J. Hostynek et al.

→
in-vitro2021

Ternary Cu2+ Complexes of Human Serum Albumin and Glycyl-l-histidyl-l-lysine

Inorganic Chemistry · K. Bossak-Ahmad et al.

→
in-vitro2024

Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro

Metallomics · J. H. Min et al.

→
animal2026

Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model

European Journal of Pharmacology · J. Hu et al.

→

Multiple entry points

Related Paths

GHK-Cu can also be explored through these curated graph routes.

No dead ends

Continue Exploring

PA

GHK-Cu Coordination & Copper Transport

pathway

Coordenação de Cu(II) por GHK e troca com proteínas transportadoras, incluindo complexos ternários com albumina; a relevância biológica depende do sistema estudado.

2 pathway7 compound15 study→
PA

Extracellular Matrix Remodeling

pathway

Rede de síntese, deposição, organização e degradação de componentes da matriz extracelular.

2 pathway7 compound15 study→
BI

Wound Healing

biological process

Inflammation, re-epithelialization, angiogenesis and tissue remodeling after injury.

4 pathway1 target7 compound15 study→
TO

Wound Healing

topic

Processo coordenado de hemostasia, inflamação, proliferação e remodelamento tecidual.

3 pathway11 compound15 study→
TO

Collagen

topic

Família de proteínas estruturais da matriz extracelular em pele, osso, cartilagem e outros tecidos.

3 pathway7 compound15 study→
PA

GHK-Cu in Wound Repair Biology

pathway

Conjunto de respostas experimentais envolvendo fibroblastos, glicosaminoglicanos, colágeno e metaloproteinases em modelos de ferida; não representa um receptor ou uma única via linear.

2 pathway7 compound15 study→
TI

Skin

tissue

Barrier organ containing epidermal, dermal, vascular and immune compartments.

4 pathway1 target12 compound15 study→
ST

Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution

study

Foundational coordination-chemistry evidence.

3 pathway7 compound14 study→

Index coverage

Literature coverage

Search updated 2026-09-02 · 15 included · 69 excluded after screening

Search strategy

PubMed

  • GHK-Cu
  • GHK Cu
  • copper peptide GHK
  • glycyl-L-histidyl-L-lysine copper
  • gly-his-lys AND copper

Inclusion criteria

  • Exact GHK-Cu complex was a primary study subject
  • Foundational copper-coordination studies
  • Biological studies with separable GHK-Cu exposure

Exclusion criteria

  • Incidental mentions
  • GHK without copper when copper-complex relevance was not separable
  • Derivatives, glycoconjugates and multicomponent formulations
  • General promotional or narrative claims

09 / References

References

  1. [1]

    J. H. Freedman, L. Pickart, B. Weinstein, W. B. Mims, J. Peisach. Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution. Biochemistry. 1982.

    DOI 10.1021/bi00262a004PubMed 6291585
  2. [2]

    J. P. Laussac, R. Haran, B. Sarkar. 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. Biochemical Journal. 1983.

    DOI 10.1042/bj2090533PubMed 6303307
  3. [3]

    F. X. Maquart, L. Pickart, M. Laurent, P. Gillery, J. C. Monboisse, J. P. Borel. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Letters. 1988.

    DOI 10.1016/0014-5793(88)80509-XPubMed 3169264
  4. [4]

    Y. Wegrowski, F. X. Maquart, J. P. Borel. Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Life Sciences. 1992.

    DOI 10.1016/0024-3205(92)90504-IPubMed 1522753
  5. [5]

    F. X. Maquart, G. Bellon, B. Chaqour, J. Wegrowski, L. M. Patt, R. E. Trachy, et al.. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. Journal of Clinical Investigation. 1993.

    DOI 10.1172/JCI116842PubMed 8227353
  6. [6]

    G. D. Mulder, L. M. Patt, L. Sanders, J. Rosenstock, M. I. Altman, M. E. Hanley, G. W. Duncan. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper. Wound Repair and Regeneration. 1994.

    DOI 10.1046/j.1524-475X.1994.20406.xPubMed 17147644
  7. [7]

    D. Godet, P. J. Marie. Effects of the tripeptide glycyl-L-histidyl-L-lysine copper complex on osteoblastic cell spreading, attachment and phenotype. Cellular and Molecular Biology. 1995.

    PubMed 8747089
  8. [8]

    A. Siméon, F. Monier, H. Emonard, P. Gillery, P. Birembaut, W. Hornebeck, F. X. Maquart. Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Journal of Investigative Dermatology. 1999.

    DOI 10.1046/j.1523-1747.1999.00606.xPubMed 10383745
  9. [9]

    A. Siméon, H. Emonard, W. Hornebeck, F. X. Maquart. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sciences. 2000.

    DOI 10.1016/S0024-3205(00)00803-1PubMed 11045606
  10. [10]

    A. Siméon, Y. Wegrowski, Y. Bontemps, F. X. Maquart. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). Journal of Investigative Dermatology. 2000.

    DOI 10.1046/j.1523-1747.2000.00166.xPubMed 11121126
  11. [11]

    L. Mazurowska, M. Mojski. ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum. Talanta. 2007.

    DOI 10.1016/j.talanta.2006.11.034PubMed 19071668
  12. [12]

    J. J. Hostynek, F. Dreher, H. I. Maibach. Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy. Inflammation Research. 2010.

    DOI 10.1007/s00011-010-0214-4PubMed 20703511
  13. [13]

    K. Bossak-Ahmad, W. Bal, T. Frączyk, S. C. Drew. Ternary Cu2+ Complexes of Human Serum Albumin and Glycyl-l-histidyl-l-lysine. Inorganic Chemistry. 2021.

    DOI 10.1021/acs.inorgchem.1c03084PubMed 34730942
  14. [14]

    J. H. Min, H. Sarlus, R. A. Harris. Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro. Metallomics. 2024.

    DOI 10.1093/mtomcs/mfae019PubMed 38599632
  15. [15]

    J. Hu, C. Zhang, F. Wang. Glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) Attenuates CuSO4 or LPS induced-inflammation in Zebrafish larvae model. European Journal of Pharmacology. 2026.

    DOI 10.1016/j.ejphar.2026.178880PubMed 41997403