Educational reference. Research use only.
GHK-Cu: Mechanism, Research, and Regulatory Status
GHK-Cu is a naturally occurring copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine (Gly-His-Lys), CAS 49557-75-7, molecular weight 403.93 Da. The published evidence for GHK-Cu is cell-culture, gene-expression and preclinical animal work, alongside its long use in cosmetic formulations; no human clinical trial is listed. GHK-Cu has no approved therapeutic indication and is supplied for research use only.
Last reviewed 2026-09-29
What is GHK-Cu?
GHK-Cu key facts
GHK-Cu is the copper(II) complex of glycyl-L-histidyl-L-lysine, a tripeptide with CAS number 49557-75-7 and a molecular weight of 403.93 Da. Pickart and Thaler first isolated GHK from human plasma albumin in 1973, and plasma levels of about 200 ng/mL in young adults are reported to decline with age. GHK-Cu holds Cu(II) through the histidine imidazole nitrogen and the N-terminal amine, and is described as a copper carrier for enzymes such as lysyl oxidase and superoxide dismutase. Maquart and colleagues reported in FEBS Letters in 1988 that GHK-Cu stimulated collagen synthesis in fibroblast cultures. A Connectivity Map analysis summarized by Pickart and Margolina in 2018 linked GHK to expression changes in over 4,000 human genes. No human clinical trial is listed for GHK-Cu; its published evidence base is in vitro, gene-expression and preclinical wound-healing work. GHK-Cu is used in cosmetic formulations, has no approved therapeutic indication, and is supplied for research use only.
How does GHK-Cu work?
GHK-Cu (glycyl-L-histidyl-L-lysine copper(II)) is a naturally occurring copper-binding tripeptide, first isolated from human plasma albumin by Pickart and Thaler in 1973. It is present at concentrations of ~200 ng/mL in plasma of young adults, and declines substantially with age. The peptide holds Cu(II) through the histidine imidazole nitrogen and the N-terminal amine in a square planar complex.
That copper binding is central to GHK-Cu's biological activity. The copper-peptide complex acts as a cellular copper chaperone, a carrier that hands copper to the enzymes that need it, including lysyl oxidase (collagen cross-linking), superoxide dismutase (SOD1), and cytochrome c oxidase. At the cellular level, GHK-Cu activates several signaling pathways at once.
It increases synthesis of collagen types I, III, and VI in dermal fibroblasts, the skin cells that build connective tissue. It also stimulates production of glycosaminoglycans and proteoglycans and promotes fibronectin and decorin expression. These are all components of extracellular matrix remodeling, the rebuilding of the scaffold between cells.
It modulates matrix metalloproteinase (MMP) activity in both directions: it increases MMP-2 and MMP-9 to clear damaged matrix, while also raising TIMP-1 and TIMP-2 to keep that remodeling in check. Gene expression analysis (Connectivity Map) shows GHK can modulate expression of over 4,000 genes, including pathways involved in inflammation (NF-κB suppression), oxidative stress (Nrf2 activation), and DNA repair. In wound healing models, GHK-Cu stimulates angiogenesis (the growth of new blood vessels) via VEGF upregulation and speeds up keratinocyte migration.
What has research on GHK-Cu found?
What published peer-reviewed research and preclinical studies have established about GHK-Cu:
- 01Naturally occurring copper-binding tripeptide found in human plasma (~200 ng/mL), saliva, and urine; concentrations decline with age
- 02In vitro: stimulates collagen I, III, and VI synthesis in dermal fibroblasts; increases GAG and fibronectin production
- 03Connectivity Map analysis (Lamb 2007): GHK modulates >4,000 human genes including NF-κB, Nrf2, TGF-β, and VEGF pathways
- 04Preclinical wound healing models demonstrate accelerated re-epithelialization, angiogenesis (via VEGF), and anti-inflammatory activity
- 05Acts as copper chaperone: delivers Cu(II) to lysyl oxidase (collagen cross-linking), SOD1 (antioxidant), and cytochrome c oxidase (mitochondrial function)
- 06Widely used in cosmetic formulations; no human clinical trial is listed among the references, so the evidence summarized here is in vitro and preclinical
- 07Anti-inflammatory activity: reduces TNF-α, IL-6, and IL-1β; suppresses NF-κB activation in macrophage and fibroblast models
Which studies have examined GHK-Cu?
GHK-Cu and collagen production (in vitro)
In vitro / mechanistic · 2015GHK-Cu (10 nM–10 μM) increased collagen synthesis 2–6x baseline in primary human dermal fibroblasts; dose-dependent response; no cytotoxicity
Gene expression network analysis
Bioinformatic / in vitro · 2018GHK regulates 4,096 human genes in the NCBI Connectivity Map; top pathways: DNA repair, ubiquitin, cancer suppressor activation, antioxidant defense, anti-inflammatory
Frequently asked questions about GHK-Cu
What is the difference between GHK and GHK-Cu?+
GHK refers to the free tripeptide (glycyl-histidyl-lysine). GHK-Cu is the copper-complexed form, where Cu(II) is coordinated in a square planar arrangement with the histidine imidazole nitrogen and N-terminal amine. Most published research uses the copper complex (GHK-Cu), which is biologically active. The free peptide (GHK) has high copper affinity and rapidly chelates available copper; commercial research preparations are typically sold as the copper complex.
How should GHK-Cu be stored?+
Store lyophilized GHK-Cu at -20°C in a sealed, desiccated vial, protected from light. Avoid repeated freeze-thaw cycles.
What does the blue-green color of GHK-Cu indicate?+
The characteristic blue-green color is caused by the Cu(II) d-d electronic transition in the square planar coordination complex. This is expected and indicates intact copper chelation. A colorless solution may suggest the copper has dissociated or the compound is the free peptide without copper. Color intensity is proportional to concentration.
Is GHK-Cu being studied for wound healing in human trials?+
Most wound healing data for GHK-Cu is preclinical (animal models, in vitro). GHK-Cu is used in cosmetic products, but no human clinical trial is listed among the references here, and no Phase 2/3 randomized controlled trials have evaluated GHK-Cu for wound healing in humans to date.
What gene pathways does GHK-Cu modulate?+
Connectivity Map analysis identified GHK as one of the most broadly acting peptides in the human transcriptome, affecting over 4,000 genes. Key pathways include: NF-κB suppression (anti-inflammatory), Nrf2 activation (antioxidant), TGF-β signaling (collagen production), VEGF upregulation (angiogenesis), ubiquitin-proteasome pathway (protein degradation/clearance), and multiple DNA damage response and repair genes. This breadth of activity underlies research into diverse applications from skin aging to potential neuroprotection.
How does GHK-Cu's activity change with age?+
Plasma GHK levels decline from ~200 ng/mL in young adults to <80 ng/mL by age 60. This age-related decline parallels decreases in skin collagen content, wound healing capacity, and antioxidant defenses. Pickart and colleagues have proposed that GHK supplementation may help restore some of these age-related deficits, though large prospective human trials testing this hypothesis have not been completed.
Is GHK-Cu approved or regulated as a drug?+
GHK-Cu is not approved as a pharmaceutical drug by the FDA. It is used widely in cosmetic products, where its safety at cosmetic concentrations is well established. As a research material, GHK-Cu falls under research chemical regulations and is not subject to pharmaceutical approval requirements. It does not appear on WADA prohibited lists.
References & sources
Every citation below was resolved against its primary source before publication. Each PMID was checked against its PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.
- [1]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
- [2]Pickart L, Vasquez-Soltero JM, Margolina A. GHK-Cu may prevent oxidative stress in skin by regulating copper and modifying expression of numerous antioxidant genes. Cosmetics. 2015. DOI: 10.3390/cosmetics2030236
- [3]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
- [4]Lamb J. The Connectivity Map: a new tool for biomedical research. Nature Reviews Cancer. 2007. PMID: 17186018 DOI: 10.1038/nrc2044
- [5]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
- [6]Buffoni F, Pino R, Dal Pozzo A. Effect of tripeptide-copper complexes on the process of skin wound healing and on cultured fibroblasts. Archives Internationales de Pharmacodynamie et de Thérapie. 1995. PMID: 8836453
Where this data comes from
- Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
- Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
- Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes often, so check FDA directly before relying on it.
- Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis. General handling is covered in the storage and stability guide.
Content last reviewed 2026-09-29. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers. It is not medical advice, and it describes no human use.
Is GHK-Cu approved for human use?
GHK-Cu is widely used in cosmetic formulations and is not classified as a pharmaceutical drug. GHK-Cu has no approved therapeutic indication. It does not appear on WADA prohibited substance lists. Supplied for research purposes only.
Research-use-only material
Specifications and certificate of analysis
GHK-Cu is stocked as a research reagent. The most recent batch (2026-03) was analysed by Janoshik Analytical at 99.533% purity; the signed certificate is published in full.