Hexapeptide-11 (Peptamide-6): yeast-derived skin peptide for cosmetics
A six-amino-acid peptide used in skincare, claimed to strengthen the skin barrier; cosmetic ingredient only, not an approved drug.
- Class
- Cosmetic peptide / proteostasis modulator
- Status
- No approved therapeutic status. Cosmetic ingredient only.
- Best-supported effect
- Proteasome, autophagy, chaperone, and Nrf2 antioxidant pathway upregulation in cultured human diploid fibroblasts (in vitro); suppression of oxidative-stress-induced premature senescence in cell models
- Main caveat
- No published human RCT data for topical Hexapeptide-11 on measurable skin outcomes; evidence base is dominated by a single research group's in vitro and ex vivo work
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: Cosmetic peptide / proteostasis modulator
Evidence tier: In vitro / assay evidence
Status: No approved therapeutic status identified. Cosmetic ingredient only.
Best-supported effect: Proteasome, autophagy, chaperone, and Nrf2 antioxidant pathway upregulation in cultured human diploid fibroblasts (in vitro); suppression of oxidative-stress-induced premature senescence in cell models
Main caveat: No published human RCT data for topical Hexapeptide-11 on measurable skin outcomes; evidence base is dominated by a single research group's in vitro and ex vivo work
What this is
Hexapeptide-11 (FVAPFP; also known as Peptamide-6) is a synthetic six-residue peptide originally isolated from yeast (Saccharomyces cerevisiae) extracts and now produced synthetically for use as a cosmetic ingredient. It is used topically in serums and anti-aging formulations.
Its proposed mechanism distinguishes it from most cosmetic peptides: rather than mimicking a neurotransmitter fragment, a collagen propeptide, or targeting a pigmentation enzyme, Hexapeptide-11 is framed as a proteostasis modulator — one that activates the cellular protein quality-control machinery in skin fibroblasts. The primary evidence for this comes from in vitro studies in cultured human diploid fibroblasts and ex vivo skin deformation assays. Whether these in vitro effects translate to measurable skin benefit in controlled human studies has not been established.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None identified | No published human RCT measuring objective skin outcomes for Hexapeptide-11 in isolation; no human trial data present in source |
| Animal | None identified | Mechanism work reported in available literature is primarily in human fibroblast cell culture rather than animal skin models |
| In vitro | Moderate | Proteasome, autophagy (BECN1, SQSTM1/p62, HDAC6), molecular chaperone (HSF1, HSP27, HSP70, HSP90, clusterin), and Nrf2-ARE pathway upregulation in human diploid fibroblasts; suppression of oxidative-stress-induced premature senescence; ex vivo elasticity improvement in skin deformation assays |
| Computational | None identified | No computational evidence in source |
| Mechanism | Plausible | Proteostasis decline is a recognized hallmark of cellular aging; the in vitro targets are mechanistically coherent. Primary receptor or binding partner mediating the broad transcriptional response is not fully characterized. |
The bulk of the in vitro and ex vivo evidence derives primarily from one published study (Gonos group, 2015); independent replication depth is a key limitation of the current evidence base.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Proteasome, autophagy, and Nrf2 pathway upregulation in cultured skin fibroblasts | Supported (in vitro) | In vitro | Medium — single primary study; independent replication limited |
| Suppression of oxidative-stress-induced premature cellular senescence | Supported (in vitro) | In vitro | Medium — cell culture model; in vivo translation not established |
| Improvement in skin elasticity | Weak (ex vivo) | In vitro | Low — ex vivo deformation assay only; not established in controlled human studies |
| Topical anti-aging benefit in humans (measurable wrinkle depth, elasticity, collagen density) | Not established | None — no human trial data in source | High — published literature explicitly identifies absence of human RCT data |
Assay conditions
This section reports conditions used in assays. It does not establish animal or human exposure.
| Context | System | Assay condition | Timepoint | Endpoint | Limitation |
|---|---|---|---|---|---|
| In vitro cell assay | Normal human diploid fibroblasts | Peptide exposure; dose- and time-dependent response reported | not individually extracted | Proteasomal subunit expression and peptidase activity, autophagy gene expression (BECN1, SQSTM1/p62, HDAC6), chaperone expression (HSF1, HSP27, HSP70, HSP90, CLU), Nrf2 nuclear accumulation, ARE target activation, senescence suppression | Cell culture model; in vivo or human translation not established; exact concentrations and timepoints not individually extracted |
| Ex vivo skin assay | Excised human skin tissue (deformation assay) | Topical application; exact conditions not individually extracted | Not individually extracted | Biomechanical elasticity | Ex vivo model; gap between ex vivo and controlled clinical measurement not bridged in source |
Assay limitations
- In vitro and ex vivo data do not establish whether the peptide penetrates the stratum corneum and reaches dermal fibroblasts at biologically active concentrations after topical application in humans.
- The evidence base is dominated by a single research group; independent replication depth is limited.
- No animal toxicology or systemic safety data are present in available literature.
- No controlled human safety or efficacy study data are present in available literature.
- The primary cell surface receptor or binding partner mediating the broad transcriptional effects reported in fibroblasts is not definitively characterized.
- Long-term effects of sustained proteasome and autophagy upregulation in skin cells have not been established in available literature.
Mechanism
Hexapeptide-11 (FVAPFP) has been characterized primarily through in vitro studies in human diploid fibroblasts. Exposure to the peptide produces dose- and time-dependent upregulation of four interconnected proteostasis systems: (1) proteasomal subunit expression and peptidase activities, promoting degradation of damaged or oxidized proteins; (2) the autophagy-lysosome system, including genes BECN1, SQSTM1 (p62), and HDAC6, supporting turnover of protein aggregates and damaged organelles; (3) molecular chaperones HSF1, HSP27, HSP70, HSP90, and clusterin (CLU), which refold or escort damaged proteins; and (4) Nrf2 nuclear accumulation with downstream antioxidant response element (ARE) target gene activation.
The net cellular effect reported in available literature is suppression of oxidative-stress-induced premature senescence and improved proteostasis capacity in fibroblast culture models. Ex vivo skin deformation assays suggest these cellular changes may associate with improved biomechanical elasticity.
The cellular receptor or primary target protein mediating these broad transcriptional effects is not fully established in available literature. Whether Hexapeptide-11 binds a specific surface receptor, translocates into cells, or acts via indirect surface engagement is not definitively characterized. The proposed proteostasis-modulation framing is mechanistically plausible given that proteostasis decline is a recognized hallmark of cellular aging, but the in vitro mechanism has not been confirmed in human tissue or clinical endpoint studies.
Chemistry
| Field | Value |
|---|---|
| Sequence (one-letter) | FVAPFP |
| Sequence (full name) | Phe-Val-Ala-Pro-Phe-Pro |
| Length | 6 amino acids |
| Topology | Linear |
| Modifications | None reported in source; standard L-amino acid composition assumed |
| Origin | Originally isolated from Saccharomyces cerevisiae (yeast) extracts; produced synthetically for cosmetic use |
| Molecular weight | Not individually extracted from source |
| Formula | Not individually extracted from source |
| CAS | Not individually extracted from source |
| Sequence confidence | Verified (sequence is consistently reported as FVAPFP across source) |
Open questions
- Human translation: No published human RCT measuring objective skin outcomes (wrinkle depth, elasticity via cutometer, collagen density) for topical Hexapeptide-11 in isolation is present in available literature. Whether the in vitro proteasome/autophagy/Nrf2 findings translate to measurable human skin benefit remains an open question.
- Skin penetration: The peptide must cross the stratum corneum to reach dermal fibroblasts. Bioavailability after topical application under realistic formulation conditions is not established in available literature.
- Primary target: The cellular receptor or binding partner that initiates the broad transcriptional response has not been definitively identified. Clarifying the primary target would strengthen mechanistic confidence and enable structure-activity optimization.
- Independent replication: The published evidence derives primarily from one research group (Gonos et al., 2015). Independent laboratory replication of the key in vitro findings is a key unresolved gap.
- Long-term safety: Effects of sustained proteasome and autophagy upregulation in skin cell populations over extended topical use are not characterized in available literature.
- Optimal concentration: The in vitro dose-response relationship has not been translated to a topical formulation concentration associated with clinical benefit; source notes optimal topical concentration remains unknown.
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.
If the peptide sticks to collagen in the deeper skin layer instead of washing away, could a single application last much longer?
If true, anti-aging creams and therapeutic skin gels would need fewer applications to work, improving convenience and lowering cost for users. It could also become a general method for making other short peptides last longer in tissue.
If it helps cells clean up their internal waste, might it also reduce the inflammatory signals that make old skin look and act older?
If true, it could become a therapy for inflammatory skin conditions linked to aging, not just a cosmetic cream ingredient. Older adults and people with chronic skin inflammation might see real clinical benefit.
If skin fibroblasts have a special doorway for this peptide that keratinocytes and pigment cells lack, would that explain why its benefits are limited to certain skin layers?
If true, formulators would know they need to add a delivery helper to reach other skin cells, or focus the peptide on fibroblast-driven concerns like dermal aging. Developers and consumers would have more realistic expectations about where it works.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| ranking score | 0.7913084030151367 | boltz-2 |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | none_monomer |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-23 |
▸citationbibtex
@peptide{pep10768,
sequence = {FPYMVR},
target = {cosmeceutical},
author = {peptidemodel},
year = {2026},
status = {computed}
}