GHK (Tripeptide-1)

What Is GHK?

GHK is glycyl-L-histidyl-L-lysine, a three-amino-acid peptide present in human plasma, saliva and urine whose levels decline with age.^[1] This page covers the copper-free peptide, sometimes called apo-GHK or GHK basic. Its copper(II) complex, GHK-Cu, is a separate material with its own literature.

Serum GHK has been reported to average about 200 ng/mL at age 20 and about 80 ng/mL by age 60.^[2] The peptide has a very high affinity for copper and readily forms the GHK-Cu chelate, and both the free peptide and the copper complex have been described as having anti-inflammatory and tissue-remodeling properties.^[2]

Much of the GHK literature does not separate the two forms. Some reviewers propose that GHK functions in the body mainly as a complex with copper 2+.^[1] A 2026 evidence-mapping review criticized the field for treating GHK-Cu as a single active ingredient and called for explicit separation of apo-GHK, canonical GHK-Cu and other copper peptides.^[3]

In cosmetics, GHK is one of the most broadly promoted peptides for topical use, and the free peptide, its copper complex and a palmitoylated derivative (Pal-GHK) all appear in anti-wrinkle products.^[4]

Chemical Structure and Molecular Identity

GHK is a linear tripeptide of glycine, L-histidine and L-lysine with a free N-terminal amine and a free C-terminal carboxylic acid. PubChem (CID 73587) lists the molecular formula C14H24N6O4 and a molecular weight of 340.38 g/mol.

The histidine imidazole ring and the glycine amine give GHK its strong copper-binding ability. Without copper, the peptide is highly polar, with a computed XLogP of -4.4. Nuclear magnetic resonance and computational work indicate that GHK in solution adopts a quasi-folded conformation held by four intramolecular hydrogen bonds.^[5]

Key identifiers

• CAS number: 49557-75-7
• InChIKey: MVORZMQFXBLMHM-QWRGUYRKSA-N
• UNII: 39TG2H631E
• Synonyms: tripeptide-1, glycyl-histidyl-lysine, Gly-His-Lys, prezatide, liver cell growth factor

GHK has two common derivatives. Metal complexation (GHK-Cu) and attachment of a hydrophobic palmitoyl group (Pal-GHK) both increase the peptide’s skin permeability compared with the free tripeptide.^[4] The copper complex is fairly hydrophilic and still permeates the stratum corneum poorly.^[6] Other approaches under study for improving skin delivery of GHK and its derivatives include cell-penetrating peptides and microneedle pretreatment.^[4]

Research History and Development

GHK was first characterized as a growth-modulating factor and wound-healing activator, and research later expanded to skin aging, lung disease, muscle and gene expression.^[5] PubChem synonyms such as liver cell growth factor and growth-modulating peptide reflect this early framing.

Wound repair dominated the early literature. A 2015 review reported that GHK accelerated healing of skin, hair follicles, gastrointestinal tract, bone tissue and the foot pads of dogs, and induced systemic wound healing in rats, mice and pigs.^[1] A 2018 review added reports of tissue repair in lung connective tissue, liver and stomach lining.^[7]

More recent work used gene-expression data to explain GHK’s broad activity. The authors of the 2015 review state that GHK can up- and downregulate at least 4,000 human genes.^[1] Based on this body of work, GHK has been proposed as a candidate for study in skin inflammation, COPD and metastatic colon cancer.^[1] Preclinical studies since then have focused on chronic obstructive pulmonary disease (COPD), often using the copper complex rather than the free peptide.^[8][9]

Mechanisms Studied in Research

GHK is studied as a regulator of extracellular matrix turnover, a chemoattractant for repair cells, a scavenger of toxic aldehydes and, through copper binding, a modulator of oxidative stress. Most mechanistic evidence comes from cell culture and reviews of earlier work.

Matrix remodeling

GHK stimulates both synthesis and breakdown of collagen and glycosaminoglycans, and modulates both metalloproteinases and their inhibitors. It stimulates collagen, dermatan sulfate, chondroitin sulfate and the proteoglycan decorin, and attracts immune and endothelial cells to sites of injury.^[1]

Aldehyde quenching

In buffer at physiological pH, copper-free GHK formed adducts with 4-hydroxy-2-nonenal (HNE), a cytotoxic product of lipid oxidation, as confirmed by mass spectrometry and NMR. GHK was an effective HNE quencher, though significantly less potent than the reference dipeptide carnosine.^[5]

Gene and signaling pathways

Reviews describe suppression of NF-κB, DNA repair activity and activation of the proteasome system as GHK effects suggested by genetic data.^[7] Preliminary observations in aging mice suggest GHK may partially reverse cognitive impairment through anti-inflammatory and epigenetic pathways.^[2]

Key Findings From Published Studies

Findings on GHK come mainly from cell and animal studies, and many of the most detailed experiments used GHK-Cu rather than the copper-free peptide. Results are grouped below by model and form.

Cell studies summarized in reviews

Reviews report that GHK stimulates blood vessel and nerve outgrowth, increases collagen, elastin and glycosaminoglycan synthesis and supports dermal fibroblast function.{c(‘gene’)} GHK has also been reported to restore replicative vitality to fibroblasts after radiation therapy.{c(‘pick’)} The same reviews list anti-inflammatory, anti-cancer and lung-protective activities, including restoration of COPD fibroblasts, largely from laboratory work.{c(‘gene’)}

Human observational data

In a small clinical comparison, plasma GHK measured by reversed-phase HPLC was lower in patients with COPD (about 70 ng/mL) than in age-paired healthy subjects (about 133 ng/mL), and levels correlated with pectoralis muscle area.^[8]

Animal and cell studies using GHK-Cu

• Skeletal muscle: GHK-Cu rescued cigarette smoke extract-induced dysfunction in C2C12 myotubes and reduced muscle mass loss in cigarette smoke-exposed mice, through a sirtuin 1-dependent pathway.^[8]
• Lung: in mice exposed to cigarette smoke for 12 weeks, GHK-Cu attenuated emphysema, partially reversed the MMP-9/TIMP-1 imbalance and reduced IL-1β, TNF-α and NF-κB.^[9]

Cosmetic and clinical evidence

Reviewers conclude that cellular studies support GHK as an anti-wrinkle ingredient, but note a surprising absence of clinical studies of GHK-Cu and Pal-GHK.^[4] The 2026 evidence map found that preclinical data consistently support effects on matrix remodeling, epithelial repair, inflammatory and redox regulation and angiogenesis, but that clinical evidence is sparse and below current active-entity quality standards, with historical cosmetic reports small or incompletely characterized and a 13-participant post-CO2-laser study reported as negative.^[3]

Because GHK and GHK-Cu are often confused, researchers typically confirm whether material is copper-free by checking HPLC and mass spectrometry certificates of analysis.

Because GHK and GHK-Cu are often confused, researchers typically confirm whether material is copper-free by checking HPLC and mass spectrometry certificates of analysis.

Regulatory and Research Status

GHK is not approved by the FDA as a drug; it is used as a cosmetic ingredient under the INCI name tripeptide-1. Its copper complex, GHK-Cu, is grouped with unapproved peptides marketed directly to patients in a 2026 sports medicine review, which notes that rigorous human safety data for such peptides are scarce.^[10]

Open questions remain about skin penetration and about which form is active. Reviewers have called for better methods to measure permeation of GHK-Cu from liposomes and other carriers.^[6] The 2026 evidence map recommends that future studies define the active entity precisely, including copper occupancy and speciation.^[3]

Copper-free GHK is supplied as a research chemical for laboratory use. Researchers studying copper-dependent effects often prepare or source the copper complex separately and verify its composition.