Hexapeptide-11

Hexapeptide-11 is a synthetic hexapeptide with the amino acid sequence phenylalanine-valine-alanine-proline-phenylalanine-proline (FVAPFP; CAS 161258-30-6; molecular formula C36H48N6O7; PubChem CID 24998056). It was originally isolated from Saccharomyces cerevisiae yeast fermentation extracts and is subsequently produced by solid-state peptide synthesis to achieve cosmetic-grade purity; the yeast-derived designation reflects its biological origin rather than the final manufacturing route.

Its primary documented mechanism involves activation of the cellular proteostasis network. In human diploid fibroblasts, exposure to the peptide produces dose- and time-dependent upregulation of four overlapping cytoprotective systems: • Ubiquitin-proteasome pathway (catalytic subunits beta1, beta2, beta5; regulatory subunits rpn6, rpn11), with measurable increases in proteasome peptidase activities after 48-72 hours • Macroautophagy (becn1, sqstm1, hdac6, and cathepsin-family genes) • Molecular chaperones (hsf1, hsp27, hsp70, hsp90, clusterin) • Nrf2-Keap1 antioxidant axis, including enhanced nuclear accumulation of Nrf2 and upregulation of nqo1 and txnrd1

A second mechanism involves senescence modulation. At concentrations of 0.1%-1.0%, the peptide reversibly downregulates ATM kinase and p53, central gatekeepers of the DNA-damage response and replicative senescence, and inhibits H2O2-induced induction of p53 and its downstream target p21CIP1. Suppression was described as concentration-dependent and reversible on washout. Manufacturer gene microarray data additionally report upregulation of the androgen receptor (AR) gene in dermal fibroblasts, which has been proposed to relate to hair follicle biology, but this claim has not been independently replicated in peer-reviewed work.

The published evidence for Hexapeptide-11 rests on two peer-reviewed laboratory studies and one small in vivo human assessment. No large randomized controlled trials, systematic reviews, or regulatory clinical dossiers have been published as of 2026.

Gruber et al. (2013; Journal of Cosmetic Science, 64:79-87; PMID 23578831) studied FVAPFP at 0.1%-1.0% in human dermal fibroblasts and dermal papilla cells in vitro. The investigators demonstrated reversible, dose-dependent downregulation of ATM and p53 protein expression and interpreted this as evidence that the peptide could modulate the onset of intrinsic and extrinsic cellular senescence. Effects in dermal papilla cells were cited in support of potential hair-related applications, though no clinical hair growth data were reported.

Sklirou et al. (2015; Redox Biology, 5:205-215; PMID 25974626; DOI 10.1016/j.redox.2015.04.010) provided a broader mechanistic characterization using IMR-90 human lung fibroblasts and normal human dermal fibroblasts. The peptide protected cells from hydrogen peroxide-induced premature senescence and activated proteasomal, autophagic, chaperone, and Nrf2-mediated antioxidant gene programs. An in vivo arm enrolled 25 volunteers who applied a firming toner containing 2.8% (v/v) Hexapeptide-11 stock solution twice daily to periocular and cheek skin for four weeks. Cutometer SEM 575 measurements showed a statistically significant improvement in Ue (initial elastic response; P less than 0.05) versus a control toner; the Uf parameter (total deformation) did not reach significance. The authors characterized the compound as a promising anti-aging agent.

All human data derive from this single small controlled comparison (n = 25). Findings are preliminary and cannot be generalized without replication in larger, rigorously randomized trials.

Typical dosage: Topical formulation (daily).

Hexapeptide-11 has no pharmaceutical or therapeutic dosing regimen. It is classified solely as a cosmetic skin-conditioning ingredient, and all concentration references below reflect cosmetic application.

In the only published in vivo human study (Sklirou et al., 2015), the test preparation was a firming toner containing 2.8% v/v of a Hexapeptide-11 stock solution, applied twice daily to the periocular and cheek area for four weeks. The pure-peptide equivalent concentration within this formulation was not specified by the authors, and the stock solution's actual peptide concentration was not disclosed.

In vitro experimental concentrations ranged from 1%-5% v/v of stock solution for gene expression and proteostasis studies, and 0.1%-1.0% for ATM/p53 modulation assays (Gruber et al., 2013).

Commercial ingredient suppliers (including Active Peptide Company and Creative Peptides) recommend finished-product usage levels of approximately 0.001%-0.01% active peptide in cosmetic formulations, consistent with the trace quantities typical of signaling peptides in marketed serums and creams. A pre-diluted 0.2% aqueous solution is available to formulators from at least one distributor. No oral, injectable, or systemic administration route has been investigated in any published source.

This information is educational and reflects concentrations described in peer-reviewed literature and ingredient-supplier guidelines. It is not medical or prescribing advice. Formulation decisions should be reviewed by a qualified cosmetic chemist or regulatory professional.

No compound-specific stability data has been identified for this peptide. The general lyophilized-peptide handling framework applies — see Storage & handling for temperature, reconstitution diluent, and beyond-use dating principles.

No peer-reviewed literature formally investigates Hexapeptide-11 in combination with other cosmetic actives. All pairings described below are based on commercial formulation practice and are anecdotal.

• Hyaluronic acid: Frequently co-formulated in serums and essences. Both ingredients are described as supporting dermal hydration and extracellular matrix integrity; compatibility in aqueous vehicles is well established commercially. Synergy is anecdotal.

• Retinol: Products from brands including Alastin Skincare include retinol alongside Hexapeptide-11. Retinol drives retinoic acid receptor signaling and collagen transcription via a pathway independent of Hexapeptide-11's proteostasis mechanism, suggesting potential additive benefit. No controlled combination study exists.

• Niacinamide and antioxidants (ascorbic acid, tocopherol): Commonly present in multi-ingredient anti-aging serums; any synergy with Hexapeptide-11 is speculative and anecdotal.

• Multi-peptide complexes (palmitoyl tripeptide-1, palmitoyl tetrapeptide-7, acetyl hexapeptide-3): Found in multi-peptide firming formulations; the rationale is additive support of collagen and matrix synthesis through mechanistically distinct signaling pathways. No comparative efficacy data exist.

Hexapeptide-11 is not currently FDA-approved for any indication. It is generally classified as a research compound. Regulatory status varies by country.

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Reported side effects: Topically safe

Hexapeptide-11 demonstrated no significant cytotoxicity in normal human diploid fibroblasts across the concentration range studied (Sklirou et al., 2015). No adverse events were reported among the 25 volunteers in the four-week in vivo application study. No published case reports of allergic contact dermatitis, irritant contact dermatitis, or sensitization specifically attributable to Hexapeptide-11 were identified in the literature search.

The peptide is composed of naturally occurring amino acids (phenylalanine, valine, alanine, proline) and is not anticipated to be a strong sensitizer on structural grounds; nevertheless, individual hypersensitivity reactions are possible with any topical ingredient, and patch testing is prudent for sensitive-skin individuals.

One mechanistic safety consideration merits acknowledgment: the reversible in vitro downregulation of p53 and ATM at 0.1%-1.0%. p53 is a tumor suppressor gene, and repeated topical modulation of this pathway, though characterized as transient and concentration-dependent, has not been evaluated over extended human use periods. The clinical significance of these in vitro observations at real-world cosmetic concentrations (estimated 0.001%-0.01% in finished products) is unknown.

Hexapeptide-11 is not listed as restricted or prohibited under EU Cosmetics Regulation (EC 1223/2009) or on the US FDA's list of prohibited cosmetic ingredients. No Cosmetic Ingredient Review (CIR) Expert Panel monograph specifically covering Hexapeptide-11 as a standalone ingredient was identified. EWG Skin Deep rates it as low concern overall, noting data gaps rather than confirmed hazards.