AHK-Cu

AHK-Cu (Ala-His-Lys copper complex, also known as Copper Tripeptide-3) is a synthetic tripeptide–copper chelate structurally related to GHK-Cu (Gly-His-Lys copper complex). It differs from GHK-Cu by a single amino acid substitution at position 1 (Ala instead of Gly), which modifies the copper chelation geometry and may alter tissue distribution and receptor engagement. AHK-Cu is used in cosmetic and hair growth formulations and is an active subject of dermatological research.

The only peer-reviewed study directly characterizing AHK-Cu is the 2007 ex vivo/in vitro hair follicle paper (PMID 17703734). No human clinical trials have been conducted. Evidence quality is limited to a single publication at cellular/tissue level.

AHK-Cu chelates copper(II) ions via the histidine imidazole nitrogen and the N-terminal amine, forming a stable square-planar copper complex consistent with the structural motif shared by GHK-Cu and other bioactive copper peptides. The copper coordination complex enables cellular uptake via copper transporter proteins (CTR1).

At picomolar to nanomolar concentrations in dermal papilla cells and hair follicles, AHK-Cu: - Stimulates DPC proliferation (Ki-67 positive cells increased) - Upregulates Bcl-2 and downregulates Bax — shifting the balance toward anti-apoptotic signaling in follicle-supporting cells - Reduces cleaved caspase-3 and PARP, confirming reduced apoptotic execution - Upregulates VEGF secretion from fibroblasts (angiogenic support for follicle vascularity) - Reduces TGF-β1 (anti-fibrotic; TGF-β1 is a known driver of follicle miniaturization in androgenetic alopecia)

The parent compound GHK-Cu has a substantially larger literature supporting wound healing, skin remodeling, and anti-inflammatory activity. AHK-Cu's single-position structural difference results in distinct copper chelation geometry that may produce different tissue distribution or receptor pharmacology, though this has not been formally characterized.