Acetyl Tetrapeptide-5

A synthetic acetylated tetrapeptide (Ac-beta-Ala-His-Ser-His-OH) developed by Lipotec as the cosmetic ingredient Eyeseryl for under-eye puffiness, with a proposed angiotensin-converting-enzyme and anti-glycation mechanism supported almost entirely by supplier in vitro data and small uncontrolled cosmetic studies.

Also referenced as: Eyeseryl

COA Public product evidence No certificate records are bound to a tracked Acetyl Tetrapeptide-5 product page A record counts here only when a vendor publishes a certificate against one of its own tracked Acetyl Tetrapeptide-5 product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

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What is Acetyl Tetrapeptide-5?

Acetyl tetrapeptide-5 is a synthetic peptide of four residues with an acetylated N-terminus and a free C-terminal acid: N-acetyl-beta-alanyl-L-histidyl-L-seryl-L-histidine (Ac-beta-Ala-His-Ser-His-OH), molecular formula C20H28N8O7, molecular weight about 492.5 Da, CAS 820959-17-9. The first residue is beta-alanine rather than a proteinogenic amino acid. The molecule was designed at the Spanish peptide manufacturer Lipotec, whose Spanish priority application of October 5, 2004 became the patent family covering it. Lipotec brought it to market in the mid-2000s under the trade name Eyeseryl as an “anti-edema” eye-contour ingredient, and it is now supplied by Lubrizol Life Science; it reaches the research-peptide market as a raw cosmetic peptide.

How it works

• Proposed angiotensin-converting-enzyme inhibition. The supplier’s rationale is that poor periorbital microcirculation contributes to under-eye bags and that a local ACE inhibitor would improve it; supplier technical literature shows a dose-dependent inhibition curve for the peptide in a cell-free ACE assay at concentrations in the microgram-to-milligram-per-milliliter range. The patent itself reports no enzyme assay and does not explain how the peptides act. The only PubMed-indexed experiment on the point is a Chinese fibroblast study that screened five cosmetic peptides, selected 100 micrograms/mL of acetyl tetrapeptide-5 as the optimal concentration for reducing angiotensin-converting-enzyme 1 activity in culture, and then tested the peptides in mixtures (Wu et al., Skin Pharmacology and Physiology, 2021;34(4):194-202). No study has shown ACE inhibition in human skin after topical application, and when the ACE claim is repeated in later industry papers it is cited to a 2017 review article rather than to primary data (Rovero et al., Clinical, Cosmetic and Investigational Dermatology, 2022;15:2693-2703).
• Proposed anti-glycation activity. Supplier literature reports that the peptide reduced non-enzymatic glycation of superoxide dismutase in vitro, preserving the enzyme’s activity, and extrapolates from this to less collagen cross-linking in the eye area. This is an in vitro observation with a single model protein; no published work has measured advanced glycation end-products in skin treated with the peptide.
• Reduced endothelial permeability in culture. In the supplier’s endothelial-monolayer insert model, the peptide is reported to have inhibited tracer leakage dose-dependently, which is the direct basis for the “anti-edema” positioning. Lubrizol’s current ingredient description frames the mechanism as inhibition of glycation, vascular permeability and lipid accumulation, all demonstrated in vitro and none published in a peer-reviewed journal.
• Classification is unsettled. A 2026 toxicology review that compiled cosmetic-peptide classifications from five earlier reviews lists acetyl tetrapeptide-5 under both “matrikine peptides” and “neurotransmitter-inhibiting peptides or peptide mimetics,” neither of which matches the enzyme-inhibitor mechanism the supplier proposes (Bjerke et al., Current Research in Toxicology, 2026;10:100291). The molecule has no sequence relationship to collagen fragments or to the SNAP-25 mimics, and its mechanism in skin has not been independently characterized.

Research status

The PubMed footprint of acetyl tetrapeptide-5 is close to empty. A title-and-abstract search for the INCI name returns a single record as of November 2026, the Wu et al. 2021 fibroblast paper above, in which the peptide was never tested in people and appeared mainly as one component of a four-peptide antioxidant mixture (carnosine, acetyl tetrapeptide-5, hexapeptide-11 and acetyl hexapeptide-3) that reduced oxidative-damage markers and raised hydroxyproline, elastin and antioxidant-enzyme activity in hydrogen-peroxide-stressed fibroblasts. A PubMed search for Eyeseryl returns no record. There is no entry for the peptide on ClinicalTrials.gov under either name.

Supplier-run volunteer studies. The human data come from Lipotec and have never been published in a peer-reviewed journal. Example 7 of the US patent (US 8,114,439, granted February 14, 2012 and reissued as USRE45610 on July 14, 2015) describes 20 volunteers with under-eye bags who applied an emulsion containing 0.01% Ac-beta-Ala-His-Ser-His-OH once daily for two months: a dermatologist judged bags reduced in 70% of volunteers at 15 days and 95% at 60 days, with instrumental readings of a 5.8% rise in skin hydration and a 35% rise in elasticity. Supplier technical sheets describe what appears to be the same study with slightly different particulars (women aged 18 to 65, twice-daily application, a four-point photographic scale against each volunteer’s own baseline). Neither description mentions a vehicle control, randomization or blinding. Supplier marketing later described a 28-day split-face study in men aged 30 to 65 who applied a cream containing 1% of the Eyeseryl solution (about 0.001% peptide) to one eye contour and a placebo cream to the other, with a reported reduction in puffiness volume of roughly 30%; the participant count, measurement method and statistics were not disclosed and the study has not been published.

Appearances in the peer-reviewed literature. Where the peptide does appear in indexed journals, it is as one ingredient among many. Rovero et al. 2022 is an industry-supported review of a skincare line whose eye contour cream pairs it with acetyl hexapeptide-8 and cross-linked sodium hyaluronate; the paper’s one sentence on acetyl tetrapeptide-5 cites a 2017 review article, and no study in it isolates the peptide. Santorelli et al., Life, 2026;16(3):465 is a 19-patient case series of thread lifting combined with a cosmetic regimen from a product line whose eye contour cream contains it alongside acetyl hexapeptide-3 and cross-linked hyaluronic acid. A 2025 review table of commercial peptide products lists it in three commercial eye-area products (Badilli and Inal, Polymers, 2025;17(6):798). Kutlubay et al., Cureus, 2026;18(5):e109369 followed 40 women for ultrasound and elastography changes after injection of a CE-marked injectable device of non-cross-linked hyaluronic acid and seven amino acids whose stated composition includes an “EyeSeryl (acetyl tetrapeptide-5) complex”; the design was open-label and single-arm, and the peptide’s contribution cannot be separated from the hyaluronic acid.

Regulatory and safety review. The peptide is listed in the EU CosIng inventory with the function “humectant.” Acetyl tetrapeptide-5 has not been the subject of a published Cosmetic Ingredient Review safety assessment as of November 2026; the Expert Panel has reviewed other cosmetic peptides (acetyl hexapeptide-8 amide, palmitoyl pentapeptide-4) but not this one. Supplier dossiers describe standard cosmetic tolerance testing; no published toxicology, sensitization or penetration study exists in the indexed literature.

Common dosage forms

Acetyl tetrapeptide-5 is a topical-only compound in practice. The branded ingredient is sold to formulators as a clear aqueous peptide solution containing 0.1% peptide (1 g/L) in water and butylene glycol or in a glycerin base, and finished consumer eye creams, gels, serums and under-eye patches typically carry 0.001% to 0.01% of the peptide, declared on the ingredient panel by the INCI name. One cream listed on DailyMed declares 0.0075 mg of acetyl tetrapeptide-5 per 15 g tube. It is also sold as powder or pre-diluted topical solution, often in multi-peptide eye-area blends.

Key considerations

• Regulatory status. The Research Market status reflects that acetyl tetrapeptide-5 has no US drug approval and no registered clinical development. It is a cosmetic ingredient with no marketing application, no IND history and no compounding pathway. A DailyMed entry for an over-the-counter eye cream that names it as an active ingredient is filed under the marketing category “unapproved drug other,” a labeler self-listing that confers no approval.
• Supplier-sourced evidence. One PubMed-indexed in vitro paper, a patent example in 20 volunteers without a stated control, and a supplier-reported 28-day split-face study with undisclosed sample size are the whole efficacy record. The ACE-inhibition and anti-glycation claims rest on cell-free and cell-culture assays at concentrations (0.1 to 1 mg/mL) far above the 0.001% to 0.01% found in finished products, and no study has measured whether a hydrophilic 492 Da peptide crosses the stratum corneum of the eyelid in meaningful amounts.
• Sequence misstatements. Some listings give the sequence as Ac-Glu-Glu-Met-Gln-NH2, which is the first four residues of acetyl hexapeptide-8 (Argireline), not acetyl tetrapeptide-5; some listings give a myristoylated hexapeptide sequence under the name. The authentic structure is Ac-beta-Ala-His-Ser-His-OH (PubChem CID 11620163), with a monoisotopic mass of about 492.2 and a protonated ion near 493.2 in the patent’s own mass spectrometry. The unacetylated sequence is a separate INCI entry, “tetrapeptide-5,” and acetyl tetrapeptide-5 should not be confused with acetyl tetrapeptide-2, -3, -9, -11 or -15, which are unrelated sequences with different targets.
• Trade names and blends. Eyeseryl is a Lipotec/Lubrizol trademark for a specific 0.1% solution, not for the peptide itself. Most eye-area products combine it with other peptides, so published or marketed results for a blend say nothing about the tetrapeptide alone.
• Safety signals. No adverse-event literature exists for the peptide, which reflects the absence of study more than demonstrated safety. Topical cosmetic concentrations have raised no published irritation or sensitization reports, and the Cosmetic Ingredient Review has not evaluated it. There are no data of any kind on injected or other non-topical routes beyond its presence as a minor component in mixed-ingredient injectable devices, and nothing is known about systemic ACE inhibition if the peptide were to reach the circulation.