3AA Preclinical
Pal-AHK
The hair-follicle signal peptide — palmitoylated Ala-His-Lys that crosses the stratum corneum to suppress TGF-β1, protect dermal papilla cells from apoptosis, and upregulate VEGF-driven angiogenesis at the follicle base.
In Plain English:
Pal-AHK is Palmitoyl Tripeptide-3: the three-amino-acid sequence Ala-His-Lys (AHK) capped at its N-terminus with a 16-carbon palmitic acid tail. AHK is a copper-chelating tripeptide structurally related to GHK (Gly-His-Lys) — the difference is that alanine replaces glycine at position 1, tuning the peptide's signalling specificity toward hair follicle dermal papilla cells rather than broad fibroblast collagen synthesis. The palmitoyl group converts the otherwise hydrophilic peptide into a lipophilic molecule that partitions into the stratum corneum's lipid bilayers and diffuses to the dermis and follicular epithelium. Once there, AHK acts through two complementary pathways: it suppresses TGF-β1 — the growth factor chronically overexpressed in androgenic alopecia that drives follicle miniaturisation — and it shifts the Bcl-2/Bax apoptosis balance toward cell survival in dermal papilla cells (DPCs), the mesenchymal cell cluster at the follicle base that governs hair cycle initiation. In skin fibroblasts, AHK independently stimulates collagen type I production (up to ~300% above controls in cell assays), fibronectin, and GAG synthesis, placing it in the signal-peptide class alongside Pal-GHK. In vitro evidence for the copper-chelating form AHK-Cu (PMID 17703734, Seoul National University, 2007) is the most rigorously published dataset for this sequence: 240 occipital hair follicles from 10 volunteers tested ex vivo across 10⁻¹² – 10⁻⁹ M showed significant elongation (p < 0.001), DPC proliferation (p < 0.001), and anti-apoptotic protection (caspase-3 −42.7%, PARP −77.5%). Palmitoylation replaces copper as the delivery strategy, prioritising transcutaneous penetration over copper carrier function. No human clinical trials specific to Pal-AHK exist; all human-relevant evidence is extrapolated from AHK-Cu in vitro work and multi-ingredient cosmetic formulation studies.
Research Maturity
Preclinical (~5 PubMed results; 1 ex vivo human study + 1 review, all on AHK-Cu not Pal-AHK; no human trials+ Studies)
Focus
Cosmetic Anti-Aging
Hair & Scalp
Skin Health
Origin
The AHK tripeptide (Ala-His-Lys) was identified as a naturally occurring copper-binding motif related to the better-known GHK sequence (Gly-His-Lys). GHK was isolated from human plasma albumin by Loren Pickart in 1973; AHK was developed subsequently as a synthetic analogue designed specifically for follicular cell signalling, with alanine substituted for glycine to shift receptor selectivity. The copper-chelating form AHK-Cu was characterised in a foundational 2007 study by Pyo et al. at Seoul National University (PMID 17703734, Archives of Pharmacal Research). Palmitoylation of the AHK sequence — producing Pal-AHK (Palmitoyl Tripeptide-3, INCI name) — followed the same commercial logic applied by Sederma to GHK: coupling a 16-carbon fatty acid to the N-terminus dramatically improves stratum corneum penetration without requiring a metal co-factor. The INCI designation 'Palmitoyl Tripeptide-3' appears in EU CosIng and EWG Skin Deep databases. No single originating company analogous to Sederma/Croda for Pal-GHK has been publicly identified as the patent holder for Pal-AHK; it is manufactured by multiple cosmetic-grade peptide suppliers globally. The CIR Expert Panel addressed related palmitoyl oligopeptides in its 2012 safety review (palmit072012slr.pdf, cir-safety.org).
Mechanism
Pal-AHK operates via three documented or strongly hypothesised pathways. First, TGF-β1 suppression: AHK-Cu and related AHK sequences reduce expression of TGF-β1, the growth-inhibitory cytokine overexpressed in miniaturising follicles in androgenic alopecia and by post-mitotic dermal fibroblasts. Suppressing TGF-β1 removes a brake on DPC proliferation and hair shaft elongation, effectively creating an anagen-permissive microenvironment. Sadgrove & Simmonds (FASEB BioAdvances 2021, PMID 34377956) confirmed AHK-Cu 'yields reduced expression of TGF-β1 and increased hair shaft elongation, increased expression of vascular endothelial growth factor and reduced negative growth factors.' Second, DPC apoptosis inhibition via Bcl-2/Bax modulation: Pyo et al. (2007, PMID 17703734) demonstrated that AHK-Cu at 10⁻⁹ M elevates the Bcl-2/Bax ratio (increased anti-apoptotic protein, decreased pro-apoptotic protein), reduces cleaved caspase-3 by 42.7%, and reduces PARP cleavage by 77.5% in DPCs. The net effect is DPC survival — maintaining the signalling hub that initiates each hair growth cycle. Third, VEGF-driven angiogenesis: AHK stimulates vascular endothelial growth factor (VEGF) secretion from fibroblasts and potentially activates VEGFR2 signalling, promoting capillary formation around follicles and improving nutrient/oxygen delivery to the dermal papilla. In skin more broadly, AHK stimulates collagen type I synthesis in fibroblasts (~300% increase vs. controls reported in cell culture data), fibronectin, proteoglycan (decorin), and GAG deposition, positioning it as a dual-action skin-firmness and hair-support peptide. The palmitoyl group's primary mechanical role is stratum corneum penetration enhancement: the 16-carbon fatty acid tail embeds in skin lipid lamellae, dragging the peptide payload past the barrier. Copper-chelating capacity (via histidine and lysine residues) may additionally activate superoxide dismutase (SOD) — providing antioxidant protection in the follicular microenvironment — and may enable minor redox signalling analogous to GHK-Cu, though free palmitoylated Pal-AHK is not a copper-delivery vehicle in the same sense as AHK-Cu.
Outcome
PRIMARY SOURCE — PMID 17703734 (Pyo HK et al., Archives of Pharmacal Research, 2007; DOI 10.1007/BF02978833): Ex vivo human hair follicle organ culture study. 240 follicles from 10 healthy volunteers (aged 20–35), occipital scalp. AHK-Cu at 10⁻¹² – 10⁻⁹ M significantly elongated hair follicles (p < 0.001) and stimulated DPC proliferation (p < 0.001) in vitro. At 10⁻⁹ M: caspase-3 cleavage −42.7% (p < 0.05), PARP cleavage −77.5% (p < 0.05), Bcl-2/Bax ratio shifted pro-survival. Biphasic dose response: higher doses (10⁻⁸ – 10⁻⁷ M) inhibited growth. Conclusion: 'AHK-Cu promotes the growth of human hair follicles through stimulation of proliferation and preclusion of apoptosis of DPCs.' Note: data are for AHK-Cu (copper-complexed form), not Pal-AHK specifically; palmitoylation replaces copper with a lipid delivery tag. PRIMARY SOURCE — PMID 34377956 (Sadgrove & Simmonds, FASEB BioAdvances 2021; DOI 10.1096/fba.2021-00022; PMC8332470): Review. AHK-Cu 'yielded reduced expression of TGF-β1 and increased hair shaft elongation, increased expression of vascular endothelial growth factor and reduced negative growth factors' in vitro — corroborating the Pyo 2007 data and connecting TGF-β1 suppression explicitly to hair shaft elongation. SKIN CELL DATA (multiple cosmetic science sources, not standalone RCT): AHK in fibroblast culture shows up to ~300% increase in collagen type I synthesis vs. untreated controls, increased cell viability (neutral red uptake assay), and elevated fibronectin/GAG levels. This dataset is cited across cosmetic science literature but originates from preclinical contract research; no peer-reviewed primary journal paper has been identified as the original source for the 300% figure specifically attributed to palmitoylated Pal-AHK. COMMUNITY/PRACTITIONER SIGNAL: Hairgenetix (hairgenetix.com) published a plain-language summary of PMID 17703734 noting the biphasic dose-response and citing the anti-apoptotic mechanism as 'relevant to understanding follicle miniaturisation in pattern baldness.' Neurogán Health positions AHK-Cu as the 'hair-specific' partner to GHK-Cu in combined-peptide hair serums, reflecting commercial practitioner uptake. HairLossTalk forum thread (2024) includes 'Palmitoyl Tripeptide-1, Tripeptide (AHK)' in RevivHair ingredient breakdown — community engagement is ingredient-list-level, not outcome-reporting level. No r/Tressless, Longecity, or HairLossTalk threads with first-person Pal-AHK topical trial reports were indexed as of 2026-05-04. MULTI-INGREDIENT PALMITOYL PEPTIDE CLINICAL CONTEXT: Hahn et al. (Experimental and Therapeutic Medicine, 2016; PMID 27446338; DOI 10.3892/etm.2016.3447): 4-week twice-daily application of a cosmetic containing 1% palmitoyl oligopeptide + palmitoyl tetrapeptide-7 — wrinkles −14.07%, elasticity +8.79%, dermal density +27.63%. Not Pal-AHK specific, but establishes that palmitoyl peptide formulations produce measurable skin-structure improvements. REGULATORY: No human clinical trials registered on ClinicalTrials.gov for Pal-AHK or palmitoyl tripeptide-3 as of 2026-05-04. FDA classification: research-use only, not approved for therapeutic indication. EWG Skin Deep lists Palmitoyl Tripeptide-3 as an ingredient in commercial cosmetics (EWG ingredient ID 724973), indicating it appears in consumer products under cosmetic claims.
