AHK-Cu
AHK-Cu is the copper(II) complex of the synthetic tripeptide L-alanyl-L-histidyl-L-lysine, an analogue of the human plasma peptide GHK in which the N-terminal glycine is replaced by alanine. The metal is held by an Xaa-His-Lys chelation site — the N-terminal amine, the deprotonated first amide nitrogen and the histidine imidazole. That geometry was determined by X-ray crystallography and solution spectroscopy for the GHK complex, which is monomeric in solution and dimeric in the solid state; it is assigned to AHK by analogy rather than by direct structure determination. The published pharmacology of AHK-Cu itself is one experiment: it stimulates proliferation and opposes apoptosis in cultured human dermal papilla cells and lengthens organ-cultured human hair follicles. No medicine containing AHK-Cu has been approved by any regulator, and no clinical trial of the compound is indexed in PubMed. The literature on this specific compound is thin and confined to laboratory models.
Information on this page is provided for laboratory research reference. The compound is not a drug, supplement, or medical product, and is not for human or veterinary use, ingestion, or consumption.
No reviewed report has been published for this product family yet. The molecular values opposite are public reference data, not results measured on a CRX sample.
Browse published reports →AHK-Cu's chemistry is inseparable from the metal it carries. The Xaa-His-Lys motif binds Cu(II) with very high affinity: isothermal titration calorimetry gives conditional dissociation constants at pH 7.4 of 7.0 ± 1.0 × 10⁻¹⁴ M for the analogous peptide GHK and 2.6 ± 0.4 × 10⁻¹⁴ M for DAHK. The same coordination work found both [Cu(II)(GHK)] and [Cu(II)(DAHK)] redox-inert at moderate potentials, with [Cu(II)(GHK)] — unlike [Cu(II)(DAHK)] — reducible to Cu(I) near −0.62 V versus AgCl/Ag and releasing its copper on reduction; the equivalent measurements have not been published for AHK. The one mechanism established for AHK-Cu itself sits in cultured human dermal papilla cells, where the peptide raises the Bcl-2/Bax ratio, lowers cleaved caspase-3 and cleaved PARP, and increases proliferation — an anti-apoptotic, pro-proliferative shift in the cells that instruct hair follicle growth. A VEGF-mediated route is proposed rather than demonstrated, and neither experiment behind the proposal used AHK-Cu: the copper tripeptide GHK-Cu significantly raised VEGF and basic FGF output early after exposure in cultured human dermal fibroblasts explanted from previously irradiated head-and-neck tissue, versus untreated controls, and transgenic VEGF overexpression enlarged hair follicles in mice. AHK-Cu was not shown to induce VEGF in the follicle study, and the follicular VEGF in the mouse work was expressed by outer root sheath keratinocytes rather than by dermal papilla cells. A separate strand of work uses a vitamin C-linker conjugate of the AHK tripeptide — a different molecule from the copper complex — which engages BMP-2/Smad1/5/8 and ERK1/2-p38 MAPK signalling in cultured mouse myoblasts.1,2,3,4,5,6
Defines the molecule: the tripeptide is a high-affinity copper chelator, characterised structurally by X-ray crystallography, EPR/HYSCORE, X-ray absorption and NMR spectroscopy, and thermodynamically by isothermal titration calorimetry, for the closely related GHK and DAHK peptides. Whether AHK-Cu acts as an inert copper carrier or as a copper donor to cuproenzymes has not been established.2,3
In cultured human dermal papilla cells, AHK-Cu raises the Bcl-2/Bax ratio and reduces the cleaved forms of caspase-3 and PARP, the proposed basis for its follicle-lengthening effect.1
Proposed, not shown for AHK-Cu. Transgenic VEGF overexpression in outer root sheath keratinocytes of mouse hair follicles induced perifollicular vascularisation, accelerated regrowth after depilation and increased follicle and hair shaft size, and GHK-Cu significantly raised VEGF output early after exposure in cultured human dermal fibroblasts explanted from previously irradiated tissue. Neither experiment used AHK-Cu.4,5
Engaged by a vitamin C-linker conjugate of the AHK tripeptide in cultured mouse C2C12 myoblasts, where it amplifies BMP-2-induced osteoblast differentiation markers. Established for the conjugate, not for the copper complex.6
Skin & matrix
In ex vivo organ-cultured human hair follicles, AHK-Cu at 10⁻¹² to 10⁻⁹ M stimulated follicle elongation relative to untreated control follicles.1
In cultured human dermal papilla cells — the fibroblasts that govern follicle morphogenesis — AHK-Cu over the same 10⁻¹² to 10⁻⁹ M range increased proliferation relative to untreated cells.1
In cultured human dermal papilla cells, 10⁻⁹ M AHK-Cu raised the Bcl-2/Bax ratio and lowered cleaved caspase-3 and cleaved PARP versus untreated cells; the accompanying fall in annexin V/propidium iodide-positive apoptotic cells was not statistically significant.1
Tissue repair
In cultured mouse C2C12 myoblasts, a vitamin C-linker conjugate of the AHK tripeptide — not the copper complex — increased proliferation and amplified the alkaline phosphatase induction produced by BMP-2 alone.6
In cultured mouse C2C12 myoblasts, vitamin C-conjugated AHK increased phosphorylation and nuclear translocation of Smad1/5/8 and phosphorylation of ERK1/2 and p38, and raised BMP-2-induced mRNA for ALP, BMP-2, osteocalcin and Runx2 above BMP-2 alone.6
What investigators recorded alongside the results above, at the rates their papers state.
No human safety, tolerability or pharmacokinetic data exist for AHK-Cu. A PubMed search returns exactly one report on AHK-Cu and one on a vitamin C-linker conjugate of the AHK tripeptide, both confined to cell and organ culture; no clinical trial, whole-animal study or toxicology report is indexed. Nothing is known about systemic exposure, copper loading or local tolerance in people.1,6
not established — no human or whole-animal exposure has been reported
The vitamin C-conjugated AHK tripeptide — not the copper complex — was reported to act 'without significant cytotoxicity' in cultured mouse myoblasts6
qualitative statement only; no incidence figures, concentrations or assay results given in the abstract
- 1.The effect of tripeptide-copper complex on human hair growth in vitro. · Archives of pharmacal research · 2007 · PMID 17703734
- 2.X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties. · Chemistry (Weinheim an der Bergstrasse, Germany) · 2011 · PMID 21780203
- 3.Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine. · Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2012 · PMID 21898044
- 4.Control of hair growth and follicle size by VEGF-mediated angiogenesis. · The Journal of clinical investigation · 2001 · PMID 11181640
- 5.Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts. · Archives of facial plastic surgery · 2005 · PMID 15655171
- 6.Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells. · Differentiation; research in biological diversity · 2018 · PMID 29567599