Overview
Pal-GHK is a synthetic, lipid-modified version of the naturally occurring tripeptide GHK (glycyl-histidyl-lysine), a copper-binding peptide found in human plasma that plays a role in tissue repair and cellular signaling. The "Pal" prefix refers to palmitoyl, a fatty acid chain attached to the peptide to improve its ability to penetrate lipid-rich surfaces, which makes it of particular interest in laboratory and cosmetic research settings. It falls into the broader category of signal peptides, which are studied for their ability to influence biological processes at the cellular level, including interactions with skin-related cell lines and connective tissue components. Researchers have investigated Pal-GHK in studies examining cell behavior, extracellular matrix activity, and its interactions with copper, among other areas of inquiry. Like all compounds featured on this site, Pal-GHK is intended strictly for research purposes and is not approved for human use or consumption.
Research & Bioactivity
Pal-GHK is a palmitoylated derivative of the tripeptide glycyl-histidyl-lysine (GHK), a sequence that researchers have studied extensively in relation to skin biology, connective tissue maintenance, and cellular repair processes. Studies have examined GHK's potential role in stimulating collagen and glycosaminoglycan synthesis, with research suggesting involvement in extracellular matrix remodeling and tissue regeneration pathways. The palmitoyl modification has been of particular interest to researchers because it enhances the peptide's lipophilicity, which is relevant to studies investigating how peptide compounds interact with skin barrier models. In vitro research has investigated Pal-GHK in the context of melanin production, including work conducted in human melanoma cell lines such as A375 and the murine B16 cell line, often in combination with other compounds. Researchers have also explored the peptide's potential connections to nerve growth factor activity and anti-inflammatory signaling, areas that remain subjects of ongoing scientific inquiry. Analytical research has additionally focused on developing detection methodologies, such as LC-MS/MS techniques, to accurately quantify palmitoyl peptides including Pal-GHK within formulation matrices, reflecting its prominence as a subject of cosmetic and biochemical research.
Published Research
Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective.
Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR — 2025
INTRODUCTION: Peptides are promising and attractive anti-wrinkle active ingredients, amongst which glycyl-histidyl-lysine peptide (GHK) is one of the most broadly promoted peptide for topical application. This simple sequence of amino acid residues not only has the capability of tissue regeneration and the enhancement of collagen and glycosaminoglycans synthesis but also is able to increase nerve outgrowth and angiogenesis. Consequently, GHK has several properties, from wound healing to prevention/reduction wrinkles. GHK-Cu and Pal-GHK are metal complex and palmitoylated derivatives of GHK, respectively. Although GHK-Cu and Pal-GHK are widely used in anti-wrinkle products available on the cosmetic market, the published information on their skin permeability, effectiveness, physicochemical properties and so on is insufficient. METHODS: This review aims to highlight whether GHK is sufficiently effective on wrinkle prevention/reduction. Apart from the effectiveness, another question that is tried to be answered is whether skin permeability of GHK allows it to act as an anti-wrinkle peptide at its site of action? Skin permeation enhancement methods employed so far are also reviewed. RESULTS: Based on cellular studies, undoubtedly, GHK can be considered as an anti-wrinkle ingredient. Although GHK-Cu and Pal-GHK have been of interest as effective peptides to be incorporated in the anti-wrinkle products, there is a surprising absence of clinical studies using them. Metal complexation and chemical modification with a hydrophobic moiety increase permeability of this peptide. Besides, cell penetrating peptides seem promising to increase skin permeation of GHK and its derivatives. Skin pretreatment with microneedles also has the potential to be further studied for permeation enhancement of such peptides. As peptide ingredients, their formulation may encounter some challenges, mainly due to their hydrophilic (high aqueous solubility and low partition coefficient) and unstable nature. CONCLUSION: Although GHK-Cu and Pal-GHK are effective and relatively skin permeable, their permeability could be successfully increased using permeation enhancement methodologies.
Palmitoyl copper peptide and acetyl tyrosine complex enhances melanin production in both A375 and B16 cell lines.
Hong M, Gui Y, Xu J, Zhao X, Jiang C, et al. — 2025
Copper peptide, a low molecular weight peptide composed of glycyl-L-histidyl-l-lysine-copper, possesses anti-aging, anti-inflammatory, and wound healing properties. In this study, we investigated the effects of a combination agent CP-AcT, composed of palmitoyl copper peptide (pal-GHK-Cu) and acetyl tyrosine (N-Acetyl-l-tyrosine), on melanin production in the human malignant melanoma cell line A375 and the mouse melanoma cell line B16. Firstly, the cytotoxicity of CP-AcT at various concentrations (0-8 μg/mL) on HaCat, HFF, A375, and B16 cells was evaluated. Subsequently, the effects of the CP-AcT on tyrosinase activity both extracellular and intracellularly, as well as on melanin production in two melanoma cell lines, were evaluated under conditions that did not compromise cell viability. Additionally, quantitative gene plex (QGP) combined with branched DNA (bDNA) technology was used to analyze the effects of CP-AcT on the expression of melanin-related genes in A375 cells, with a focus on five specific genes. Finally, the effects of the CP-AcT on the expression of three proteins involved in the biosynthesis pathway of melanin: tyrosinase (TYR), dopachrome tautomerase (DCT), and endothelin 3 (EDN3) were analyzed. The results indicate that the complex CP-AcT effectively promotes melanin production in both types of melanoma cells.
Clinical assessment of a combination lip treatment to restore moisturization and fullness.
Trookman NS, Rizer RL, Ford R, Mehta R, Gotz V — 2009
Objective. To evaluate the efficacy and tolerance of a topical lip-care treatment. Step one of the two-step treatment is a lip-renewal formulation containing human growth factors, hyaluronic acid and marine filling spheres, emollients, and a tripeptide palmitoyl-glycyl-histidyl-lysine complex. Step two is a lip-plumper formulation containing niacin, emollients, and essential fatty acids. Design. Four-week, single-center, open-label, clinical study with clinical assessments at Baseline, Week 2, and Week 4. Treatment. Subjects wore the lip products at least eight hours every day with a minimum of three applications per day. Participants. Thirty-two women ages 22 to 40 years with mild-to-moderate lip dryness and average size lips completed the study. Measurements. Visual grading of the condition of the lips, rating of subjective irritation, corneometry, digital caliper measurements of lower lip, and digital photography. A self-assessment questionnaire was also employed to assess patient satisfaction. Results. Clinical assessments showed statistically significant improvements (P<0.001) in key lip condition parameters after both two and four weeks of use. Key parameters included lip scaling, cupping, cracking/fissuring, fine lines due to dryness, lip texture/visual roughness, lip color/rosiness, lip definition/contour, and overall lip condition. Significant increases (P<0.001) were observed in both corneometer measurements, which confirm the moisturizing benefits, and in digital caliper measurements, which confirm the lip-plumping benefits. Self-assessment questionnaires showed a 97-percent overall satisfaction rating. No adverse events were reported during the course of the study. Conclusion. The results from this clinical study demonstrate that this two-part lip-care treatment product was well tolerated and effective in restoring moisture and fullness to the lips of female subjects with mild-to-moderate lip dryness.
Development of a LC-MS/MS method to monitor palmitoyl peptides content in anti-wrinkle cosmetics.
Chirita RI, Chaimbault P, Archambault JC, Robert I, Elfakir C — 2009
Palmitoyl peptides are anti-aging agents widely used in cosmetics. This article describes the development of a LC-MS/MS analytical procedure that allows, after a liquid-liquid extraction procedure, their unambiguous detection in cosmetic formulation. MS/MS detection is shown to be specific regarding placebo formulations. Limits of quantification, linearity, accuracy and precision of the method were estimated. The results presented show that palmitoyl peptides can be thus reliably assayed. The palmitoylated pentapeptide palmitoyl-lysyl-threonyl-threonyl-lysyl-serine (pal-KTTKS) was assayed in anti-wrinkle creams using palmitoyl-glycyl-histidyl-lysine (pal-GHK) as internal standard. From the results obtained, the influence of the formulation on pal-KTTKS availability is evidenced.