Pal-AHK: copper-binding peptide studied for hair and skin
A lab-made cosmetic ingredient that may help boost collagen and support hair follicles; used in skincare, not an approved drug.
- Class
- Cosmeceutical lipopeptide (palmitoylated copper-binding tripeptide)
- Status
- Cosmetic ingredient; not approved as a drug in any jurisdiction
- Best-supported effect
- Dermal papilla cell anti-apoptotic signaling and hair follicle elongation in cell culture and ex vivo assay systems (AHK-Cu form only)
- Main caveat
- All biological activity evidence is in vitro and ex vivo only, using the copper-complexed form (AHK-Cu) — not the palmitoylated commercial form (Pal-AHK); no animal in vivo or human trial data exist
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Cosmeceutical lipopeptide (palmitoylated copper-binding tripeptide)
Evidence tier: In vitro / assay evidence
Status: Cosmetic ingredient; not approved as a drug in any jurisdiction
Best-supported effect: Dermal papilla cell anti-apoptotic signaling and hair follicle elongation in cell culture and ex vivo assay systems (AHK-Cu form)
Main caveat: All biological activity evidence is in vitro and ex vivo only, using the copper-complexed form (AHK-Cu) — not the palmitoylated commercial form (Pal-AHK); no animal in vivo or human trial data exist
What this is
Pal-AHK (Palmitoyl Tripeptide-28, also referenced under the older designation Palmitoyl Tripeptide-3) is a synthetic lipopeptide consisting of the tripeptide alanine-histidine-lysine (AHK) conjugated to palmitic acid at the N-terminus. The palmitoyl modification increases lipophilicity, which is intended to improve penetration through the stratum corneum in topical cosmeceutical formulations. The AHK tripeptide belongs to the copper-binding tripeptide family and forms the AHK-Cu complex (Copper Tripeptide-3) in the presence of copper ions; the copper-complexed form is the active species in all published in vitro research. Pal-AHK is structurally related to Pal-GHK (Palmitoyl Tripeptide-1), differing at the first amino acid (alanine versus glycine), but has a distinct and far thinner research profile centered on hair follicle and dermal papilla biology rather than the matrikine-driven collagen signaling associated with GHK. It is marketed as a cosmeceutical ingredient for hair growth and skin anti-aging; these commercial uses rest on a narrow preclinical evidence base.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None | No published human clinical trials for Pal-AHK or AHK-Cu for any endpoint |
| Animal | None | No published in vivo animal hair-growth or skin studies for AHK-family peptides |
| In vitro / ex vivo | Weak — single study, copper-complexed form only | Hair follicle elongation ex vivo; dermal papilla cell anti-apoptotic signaling; fibroblast collagen and VEGF responses in cell culture |
| Computational | None | No docking or structure-prediction data identified |
| Mechanism | Plausible | Anti-apoptotic Bcl-2/Bax modulation, VEGF upregulation, TGF-β1 suppression, and collagen type I stimulation are mechanistically described from the in vitro data; pathway from palmitoylated form to AHK-Cu activity is assumed, not demonstrated |
The in vitro and ex vivo evidence derives almost entirely from a single publication (Pyo et al., 2007); independent peer-reviewed replication is absent. Whether the palmitoylated commercial form (Pal-AHK) is equivalent to the copper-complexed research form (AHK-Cu) at the cellular level has not been characterized.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Hair follicle elongation and dermal papilla cell survival (ex vivo / in vitro, copper-complexed form) | Supported (in vitro / ex vivo) | In vitro | Low — single study, AHK-Cu form, not Pal-AHK; no independent replication |
| Collagen type I synthesis stimulation in fibroblast cultures | Supported (in vitro) | In vitro | Low — single study; no independent replication |
| Hair growth stimulation in living humans | Not established | None | High |
| Pal-AHK is equivalent to AHK-Cu in biological activity | Not established | None | High — assumed by commercial use but not characterized |
| Skin pigmentation and tone improvement | Not established | None | High — no peer-reviewed mechanistic data; commercially driven claim |
| Safe and effective for injectable use | Not established | None | High — cosmetic preparations are not sterile injectable products; no clinical or efficacy data exist for this route |
Assay conditions
This section reports concentrations and conditions used in the published in vitro and ex vivo assays. It does not establish topical cosmeceutical dose, frequency, or any human exposure.
| Context | System | Assay condition | Timepoint | Endpoint | Limitation |
|---|---|---|---|---|---|
| In vitro — dermal papilla cell proliferation | Human dermal papilla cells (cultured) | AHK-Cu at 10⁻¹² to 10⁻⁹ M | Not individually extracted | DPC proliferation; Bcl-2/Bax ratio; cleaved caspase-3 and PARP levels | AHK-Cu form only; not Pal-AHK; single study; concentration-to-topical-product translation not established |
| Ex vivo — hair follicle elongation | Cultured human hair follicles | AHK-Cu at picomolar to nanomolar concentrations | Not individually extracted | Follicle elongation | Ex vivo organ culture, not in vivo; AHK-Cu form only; no independent replication |
| In vitro — fibroblast collagen and VEGF | Human dermal fibroblast cultures | AHK-Cu (concentration not separately extracted) | Not individually extracted | Collagen type I (up to 300% increase reported); VEGF secretion; TGF-β1 secretion | Single study; cell culture system; AHK-Cu form; translation to topical application not established |
Assay limitations
- All published biological activity data use the copper-complexed form (AHK-Cu, Copper Tripeptide-3), not the palmitoylated commercial form (Pal-AHK, Palmitoyl Tripeptide-28). Whether Pal-AHK is cleaved to release free AHK intracellularly, or whether the intact palmitoylated molecule acts equivalently to AHK-Cu at the cell surface, has not been characterized.
- The entire hair-growth signal traces to a single publication (Pyo et al., 2007); independent peer-reviewed replication of the core findings does not appear in the available literature.
- Ex vivo hair follicle culture and in vitro DPC assays do not establish whether follicle-level effects translate to in vivo hair growth in intact skin or in human scalp.
- In vitro concentration ranges (picomolar to nanomolar for AHK-Cu) do not translate directly to topical product percentage concentrations; actual delivery of active peptide to dermal papilla cells from commercial topical formulations is not quantified.
- No formal cell-viability or cytotoxicity data beyond the proliferation endpoints are reported in available literature.
- No animal or human safety or efficacy data are identified.
Mechanism
The AHK tripeptide, in its copper-complexed form (AHK-Cu), exerts biological effects through anti-apoptotic signaling in dermal papilla cells (DPCs) and fibroblast stimulation. In dermal papilla cells, AHK-Cu elevates the Bcl-2/Bax ratio by upregulating the anti-apoptotic protein Bcl-2 and downregulating the pro-apoptotic protein Bax; it also reduces cleaved caspase-3 (by approximately 42.7% at 10⁻⁹ M) and cleaved PARP (by approximately 77.5%), indicating reduced programmed cell death. In dermal fibroblasts, AHK-Cu stimulates proliferation, elevates VEGF secretion (supporting angiogenesis and follicular vascularization), and decreases TGF-β1 secretion — TGF-β1 being a catagen-inducing factor that suppresses hair follicle cycling into the growth phase. Collagen type I production in fibroblast cultures was reported to increase substantially. The copper-coordination capacity of the AHK sequence resides in the histidine imidazole ring and the lysine amine group. The palmitoyl modification (C16 fatty acid at the N-terminus) is intended to enhance partitioning into the lipid-rich stratum corneum; whether Pal-AHK is subsequently cleaved to release biologically active AHK or copper complex intracellularly, or acts as an intact molecule at the receptor/cell surface, is uncharacterized. No receptor-level binding data exist. The mechanistic basis for marketed pigmentation claims is absent from published literature.
Chemistry
| Field | Value |
|---|---|
| Full name | Palmitoyl-Ala-His-Lys; Palmitoyl Tripeptide-28 |
| Older INCI designation | Palmitoyl Tripeptide-3 |
| Amino-acid chain | Ala-His-Lys (three residues) |
| Length | 3 amino acids |
| Topology | Linear |
| Modification | N-terminal palmitoyl group (C16 fatty acid, palmitic acid conjugation) |
| Copper-complexed form | AHK-Cu (Copper Tripeptide-3); active form used in published assay research |
| Molecular formula | C₃₁H₅₆N₆O₅ |
| Molecular weight | ~592.8 Da |
| Sequence confidence | Verified (source-consistent) |
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US | Cosmetic ingredient; not a drug | Regulated under FDA cosmetic law; over-the-counter sale in finished cosmetic formulations is permitted; not approved as a drug for hair loss, skin aging, or any medical indication; hair-loss drug claims are not permitted on cosmetic labels |
| EU | Permitted cosmetic ingredient | Listed in the CosIng database; safety reviews of related copper tripeptides and palmitoyl tripeptides have not raised concerns at typical formulation levels (per available sources) |
| UK, Canada, Australia, Japan | Permitted as cosmetic ingredient | Per available sources, broad international cosmetic market access; status not independently refreshed in this card |
| WADA | Not listed as prohibited | Topical cosmeceutical use; negligible systemic exposure relevant to performance (per available sources; current list status not independently verified in this card) |
No approved therapeutic status exists for Pal-AHK in any attached source. This card describes a cosmetic ingredient, not an approved medicine.
Open questions
- Human translation: No controlled human trials for Pal-AHK or AHK-Cu exist for hair growth, skin anti-aging, or any other endpoint. Whether the in vitro and ex vivo signals observed with AHK-Cu translate to detectable clinical benefit in humans is unknown.
- Pal-AHK vs. AHK-Cu equivalence: Whether the palmitoylated form is cleaved or otherwise converted to an active copper complex in vivo, or whether it reaches dermal papilla cells with retained bioactivity, has not been characterized. All published efficacy data use AHK-Cu, not Pal-AHK.
- Independent replication: The foundational hair-growth findings (Pyo et al., 2007) have not been independently replicated in peer-reviewed literature. The entire biological plausibility claim rests on a single research group's work.
- In vivo animal hair-growth models: No published rodent or other in vivo models have been conducted for AHK-family peptides, representing a notable gap between ex vivo organ culture and any in vivo system.
- Skin penetration and delivery quantification: Whether topical cosmeceutical formulations deliver biologically relevant concentrations of Pal-AHK or AHK to dermal papilla cells or fibroblasts in intact human skin is not established.
- Pigmentation mechanism: No peer-reviewed data demonstrate any effect of Pal-AHK or AHK-Cu on melanogenesis or melanocyte biology. The marketed pigmentation claim lacks published mechanistic basis.
- Long-term safety: Chronic topical safety under sustained use — particularly for scalp formulations — has not been formally evaluated. The long-term biology of topical copper tripeptide exposure, including cumulative copper coordination effects, is not characterized.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does attaching a fatty acid to AHK's active end, as done in the commercial product, permanently block the part of the molecule that must grab copper to function?
If the commercial formulation is inadvertently self-sabotaging, reformulating with the copper-binding end of AHK left free could dramatically improve efficacy for people using the product for hair thinning or skin care. It would also reveal that decades of cosmetic industry investment in this particular lipopeptide form may need to be redirected.
Does AHK-Cu work by catalytically dismantling the reactive oxygen species that accumulate in hair follicle cells under stress, similar to how the body's own superoxide dismutase enzyme works?
If AHK-Cu is a catalytic antioxidant, it could protect hair follicles at very low doses, making it more feasible to deliver enough of it through the skin to actually work. This would be relevant to anyone experiencing hair thinning linked to oxidative stress, including androgenic alopecia, which affects roughly half of all adults over 50.
Does the methyl group on alanine in AHK-Cu change the shape of the copper coordination complex enough to switch it from collagen-stimulating (GHK-Cu) to hair-follicle-protecting activity?
Understanding why such a tiny chemical difference between two very similar peptides produces such different results would give scientists a precise design rule for engineering copper peptides with specific skin or hair benefits on demand, potentially replacing years of empirical screening with rational design.
Could conjugating AHK to a fragment of hyaluronic acid direct the peptide specifically to the hair follicle cells that express the hyaluronic acid receptor, delivering a therapeutic dose where it is actually needed?
One of the biggest obstacles to turning AHK-Cu from a laboratory finding into a real hair-loss treatment is getting enough of it into the right place under the skin. A targeted delivery system that homes in on hair follicle cells could bridge that gap, potentially making an effective topical treatment for common hair thinning available without injections.
▸3-letter notation
▸citationbibtex
@peptide{pep10953,
sequence = {AHK},
target = {},
author = {peptidemodel},
year = {2026},
status = {designed}
}