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Tripeptide — Matrikine / Cosmetic Signaling Peptide

GHK Basic Cosmetic Only

GHK  |  Gly-His-Lys  |  Glycyl-L-histidyl-L-lysine  |  copper-free GHK  |  apo-GHK  |  CAS 49557-75-7
Sequence
Gly-His-Lys (3 aa)
Molecular Weight
340.38 g/mol
Copper Bound
No (parent GHK-Cu carries Cu²⁺)
Half-life
Minutes (plasma, extrapolated)
Route
Topical (cosmetic) / research SubQ
FDA Status
Cosmetic ingredient only
Human Trials
Topical cosmetic only
WADA Status
Not specifically named; plausibly S0 by analogy
Cost & Access
Research-only (cosmetic OTC)
TL;DR

A human plasma tripeptide from 1973. Strip the copper off, most of the published evidence goes with it.
What: The copper-free form of Gly-His-Lys. Same sequence as GHK-Cu, no chelated Cu²⁺. Endogenous to human plasma.
Does: Matrikine collagen signal, aldehyde scavenger, gene-expression modulator. In direct fibroblast assays, the apopeptide performs less strongly than GHK-Cu.
Evidence: Copper-independent evidence is thin: Choi 2012 on stem-cell preservation and Beretta 2007/2008 on aldehyde chemistry. No independent human RCT on the apopeptide.
Used by: Cosmetic formulators when copper conflicts with vitamin C or retinoids. Research-chemical channels sell the powder to the DIY community.
Bottom line: Endogenous to humans, weaker than GHK-Cu head-to-head. The copper is where the work gets done.

What It Is

GHK Basic is the copper-free form of the tripeptide glycyl-L-histidyl-L-lysine (Gly-His-Lys, or "GHK"). It has the same amino-acid sequence as GHK-Cu — the widely studied "copper peptide" used in cosmetic serums and research protocols since the 1980s — but is supplied without the coordinated Cu²⁺ ion that the parent peptide chelates with very high affinity (log cK7.4 ≈ 12.62 under physiological conditions). In chemistry terminology, GHK Basic is the apopeptide and GHK-Cu is the metallopeptide. Many vendors describe the product as "GHK," "GHK Basic," "copper-free GHK," "free GHK," or "GHK fragment."

The GHK sequence was first isolated from human plasma in 1973 by Loren Pickart, then at the University of California, San Francisco, who identified it as a small tripeptide that could promote the growth of cultured hepatoma cells and prolong the survival of normal hepatocytes (Pickart and Thaler, Nature New Biology 1973). Subsequent biochemical characterization — notably the Maquart et al. 1988 FEBS Letters paper demonstrating fibroblast collagen stimulation — was performed almost exclusively with the copper-bound form. That is why the literature, the cosmetic ingredient listings (INCI: "Copper tripeptide-1"), and the bulk of clinical interest all center on GHK-Cu rather than its copper-free counterpart.

GHK Basic became commercially interesting in the late 2000s when formulation chemists encountered practical problems combining GHK-Cu with high-concentration ascorbic acid (which reduces Cu²⁺ to Cu¹⁺ and destabilizes the complex) and with some peptide-compatible vehicles. A copper-free version solved those formulation conflicts and, in parallel, Choi et al.'s 2012 J Pept Sci paper reported that the apo-tripeptide retained meaningful biological activity in human skin-equivalent models — specifically, a stem-cell-preserving effect mediated through fibroblast-keratinocyte signaling that did not strictly require bound copper. Since then, a small body of literature has suggested that GHK and GHK-Cu share overlapping but non-identical biological profiles.

Practically, GHK Basic is used in two separate contexts: (1) as a cosmetic ingredient in topical serums and creams, where it acts as a gentle matrikine collagen signal without delivering exogenous copper; and (2) as a research peptide sold by research-chemical vendors as a less-studied sibling of GHK-Cu. Anyone choosing between the two should understand that the vast majority of published clinical and preclinical evidence uses the copper-bound form, and that under physiological conditions a copper-free GHK administered parenterally will rapidly encounter and bind endogenous copper — blurring the in-vivo distinction between "GHK" and "GHK-Cu" within minutes of administration.

Mechanism of Action

The scientifically interesting question is which GHK activities are copper-dependent and which are not. The literature supports three broad mechanistic categories for the copper-free tripeptide.

What the Research Shows

Research on the copper-free form specifically — as distinct from GHK-Cu — is thinner but not empty. The published findings that most cleanly address the copper-free case:

Research Limitation — Most Evidence Is on the Copper Form

The vast majority of GHK-family research uses the copper-bound form. Vendor marketing of copper-free GHK as a "research peptide" routinely cites GHK-Cu evidence as if it applied to the apopeptide. It does not, except in the specific cases where a study demonstrated copper-independent activity (Choi 2012 stem-cell work, the antioxidant literature, and the aldehyde-sequestration chemistry). Transfer of broad GHK-Cu claims to the copper-free form is not scientifically justified.

Human Data

There is no published clinical trial of injected or systemically dosed copper-free GHK in humans. The published human evidence base for the GHK family sits almost entirely on topical GHK-Cu cosmetic studies, none of which directly apply to parenteral copper-free GHK use.

Dosing from the Literature

No human dose-finding study has been performed for copper-free GHK. The ranges below are either cosmetic-formulation standards or extrapolations from GHK-Cu protocols. No FDA-approved dose exists.

RouteDose / ConcentrationFrequencyNotes
Topical (cosmetic serum)0.1–2% peptide in formulation1–2x dailyStandard matrikine concentration range. Compatible with high-concentration ascorbic acid and retinoids where GHK-Cu is not.
Topical (professional / intensive)2–5%Once dailyHigher-concentration leave-on products. Most topical evidence uses GHK-Cu.
Subcutaneous (community)1–3 mgOnce dailyExtrapolated from GHK-Cu community protocols. No copper-free-specific dose-response data.
Oral / sublingual (community)1–3 mgOnce dailyOral bioavailability is poor (tripeptide is degraded by gastric and intestinal proteases). Inferential only.
Cycle length (community)4–12 weeksInherited from GHK-Cu protocols. No copper-free-specific tachyphylaxis or cycling data.
Dosing Disclaimer

Copper-free GHK has never been formally dose-finding-studied in humans for any indication other than topical cosmetic formulation. Whether the copper-free form has different optimal dosing, half-life, or route preference than the copper-bound form has not been established. Anyone considering parenteral use should work with a licensed clinician.

Reconstitution & Storage

Copper-free GHK is supplied as a lyophilized powder, typically in 50 mg or 100 mg vials. Unlike GHK-Cu — which is blue-to-turquoise from the copper coordination — copper-free GHK is a colorless to off-white powder that reconstitutes to a clear, colorless solution.

Vial SizeBAC WaterConcentration1 mg Dose2 mg Dose
50 mg2 mL25 mg/mL4 units (0.04 mL)8 units (0.08 mL)
100 mg2 mL50 mg/mL2 units (0.02 mL)4 units (0.04 mL)

→ Use the Kalios Dosing Calculator for exact syringe units

Side Effects & Risks

Important

Share this with your clinician before combining GHK Basic with penicillamine, trientine, or chronic high-dose zinc — the copper-sequestration chemistry becomes clinically relevant in copper-modulating regimens.

Copper-free GHK has no published human parenteral safety data specific to the apopeptide. The inferred risk profile draws from the GHK-Cu topical record plus the specific copper-sequestration considerations.

Bloodwork & Monitoring

No formal monitoring guideline exists for copper-free GHK. Conservative monitoring mirrors GHK-Cu protocols with attention to copper homeostasis.

Commonly Stacked With

The natural comparator and the more evidence-backed alternative. Users sometimes sequentially trial copper-free GHK and GHK-Cu to compare response. Concurrent stacking is uncommon and largely redundant since both forms converge in vivo after copper coordination.

Topical retinoid (tretinoin, retinaldehyde, retinol)

The single most evidence-backed topical anti-aging intervention. Copper-free GHK is one of the few peptides that formulates cleanly in the same product as high-concentration retinoids, where GHK-Cu would be destabilized. For users targeting skin quality, a topical retinoid plus dermatologist-grade sun protection is the foundation; GHK layers on top.

Vitamin C (topical ascorbic acid)

Cofactor for collagen synthesis. Copper-free GHK tolerates ascorbic acid formulations, which is one of the main practical arguments for using the apopeptide over GHK-Cu in a combination serum.

A different matrikine peptide (palmitoyl-pentapeptide-4) that stimulates fibroblast collagen synthesis. Used together in cosmetic formulations on the logic that different matrikines engage complementary fibroblast signaling pathways.

L-carnosine (oral)

Dipeptide with overlapping aldehyde-sequestration chemistry (same histidine-mediated reactivity toward 4-HNE and acrolein). Much cheaper, oral, decades of supplement use. For users whose goal is antioxidant / anti-aging support rather than skin-specific cosmetics, carnosine is the more evidence-backed option.

→ Check compound compatibility in the Stack Builder

Regulatory Status

Current Status — April 2026

Copper-free GHK (Gly-His-Lys tripeptide) is not FDA-approved for any therapeutic indication. As a peptide, it is research-only for parenteral or systemic use. Topical use as a cosmetic ingredient is the dominant legitimate route: the copper-bound form carries the INCI designation "Copper tripeptide-1" and the copper-free form is typically labeled "Tripeptide-1" on cosmetic ingredient lists.

Parent GHK-Cu appears on FDA's compounding bulk-substance evaluation lists, with its Category designation having shifted across recent years. On February 27, 2026, HHS Secretary Robert F. Kennedy Jr. publicly announced an intention to reclassify approximately 14 of the 19 Category 2 peptides — GHK-Cu among them — back to Category 1, which would make them available through licensed compounding pharmacies with a prescription. As of April 2026, the FDA has not published a formal update and the Pharmacy Compounding Advisory Committee (PCAC) has not completed review.

The copper-free GHK form has not been specifically named in either the Category 2 list or the RFK reclassification announcement — likely because regulatory attention focuses on the well-characterized copper-bound form. If GHK-Cu is reclassified to Category 1, it is unresolved whether copper-free GHK would automatically receive the same status; the two are technically different chemical entities and each would, in principle, require its own bulk-substance evaluation.

WADA: The GHK family is not specifically named on the Prohibited List. Athletes should consult their sport-specific federation before any use; the compound does not currently have a clean fit in any named S-class but could plausibly be evaluated under broader categories.

Cost & Access

Copper-free GHK is not approved for human use as a parenteral peptide therapeutic. It is available in two legitimate channels: (1) as an ingredient in topical cosmetic products sold over the counter without prescription, typically at peptide concentrations of 0.1–2% in serums and creams; and (2) through research-chemical suppliers for laboratory research purposes only, supplied as lyophilized powder in 50 mg or 100 mg vials.

U.S. compounding pharmacies cannot legally compound copper-free GHK for parenteral use under current FDA bulk-substance rules — the apopeptide has not been specifically named on any compounding-pathway list. If the parent GHK-Cu is reclassified to Category 1 under HHS Secretary Robert F. Kennedy Jr.'s February 2026 announcement, it remains unclear whether copper-free GHK would automatically follow, since each form would, in principle, require its own PCAC evaluation.

Cosmetic topical products containing copper-free GHK are widely available in consumer skincare; the research-chemical channel is the standard route for parenteral research use. Kalios does not sell compounds.

Access and regulatory status as of April 2026. Actual availability varies by jurisdiction, channel, and prescription status. Kalios does not sell compounds.

Related Compounds

GHK-family peptides and copper-tripeptide cousins:

Fragment of the GHK-Cu molecule studied for its role in gene expression and copper delivery.

Alanine-Histidine-Lysine copper peptide. Used primarily in hair-follicle activation and topical scalp formulations.

Palmitoyl-GHK (palmitoyl tripeptide-1). Lipophilic cosmetic version of GHK for topical anti-aging formulations.

Palmitoyl tetrapeptide-7. Anti-inflammatory cosmetic peptide that reduces interleukin-6 in aging skin.

Next Steps

Key References

  1. Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nat New Biol. 1973;243(124):85-87. PMID: 4351857. (Original isolation of GHK from human plasma.)
  2. Maquart 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⁺. FEBS Lett. 1988;238(2):343-346. PMID: 3169264. (Foundational collagen-stimulation paper — copper-bound form.)
  3. Choi HR, Kang YA, Ryoo SJ, Shin JW, Na JI, Huh CH, Park KC. Stem cell recovering effect of copper-free GHK in skin. J Pept Sci. 2012;18(11):685-690. doi:10.1002/psc.2455. (Key paper for copper-free GHK: stem-cell preservation in human skin equivalents without copper coordination.)
  4. Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging. Oxid Med Cell Longev. 2012;2012:324832. PMID: 22666521.
  5. Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. PMID: 26236730.
  6. Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. Int J Mol Sci. 2018;19(7):1987. PMID: 29986520. (Comprehensive modern review; notes copper-dependent vs copper-independent activities.)
  7. Pickart L, Vasquez-Soltero JM, Pickart FD, Majnarich J. GHK, the Human Skin Remodeling Peptide, Induces Anti-Cancer Expression of Numerous Caspase, Growth Regulatory, and DNA Repair Genes. J Anal Oncol. 2014;3(2):79-87.
  8. Beretta G, Aldini G, Facino RM, Russell RM, Krinsky NI, Yeum KJ. Glycyl-histidyl-lysine (GHK) is a quencher of α,β-4-Hydroxy-trans-2-nonenal: a comparison with carnosine. Insights into the mechanism of reaction by ESI-MS, ¹H NMR, and computational techniques. Chem Res Toxicol. 2007;20(9):1309-1314. doi:10.1021/tx700185s. (Copper-independent aldehyde-sequestration chemistry.)
  9. Beretta G, Arlandini E, Artali R, Anton JM, Maffei Facino R. Acrolein sequestering ability of the endogenous tripeptide glycyl-histidyl-lysine (GHK): characterization of conjugation products by ESI-MSn and theoretical calculations. J Pharm Biomed Anal. 2008;47(3):596-602.
  10. Trapaidze A, Hureau C, Bal W, Winterhalter M, Faller P. Thermodynamic study of Cu²⁺ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine. J Biol Inorg Chem. 2012;17(1):37-47. PMID: 21748269. (Quantifies the very high copper-binding affinity that drives in-vivo coordination after administration.)
  11. Pickart L, Freedman JH, Loker WJ, Peisach J, Perkins CM, Stenkamp RE, Weinstein B. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980;288(5792):715-717. PMID: 7432330.
  12. Pickart L, Vasquez-Soltero JM, Margolina A. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline. Brain Sci. 2017;7(2):20. PMID: 28212278.
  13. Hostynek JJ, Dreher F, Maibach HI. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflamm Res. 2011;60(1):79-86. PMID: 20835751. (Topical penetration data — relevant to cosmetic copper-free formulations.)
  14. Pollard JD, Quan S, Kang T, Koch RJ. Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. Arch Facial Plast Surg. 2005;7(1):27-31. PMID: 15655171.
  15. Gruchlik A, Jurzak M, Chodurek E, Dzierzewicz Z. Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on TNF-alpha-dependent IL-6 secretion in normal human dermal fibroblasts. Acta Pol Pharm. 2012;69(6):1303-1306. PMID: 23285693.
  16. FDA. Bulk Drug Substances Nominated for Use in Compounding — 503A and 503B Categories. FDA.gov. Updated 2025-2026.
  17. WADA Prohibited List 2026. World Anti-Doping Agency. wada-ama.org.

Last updated: April 2026  |  Profile authored by Kalios Peptides research team