SNAP-8 (Acetyl Octapeptide-3)

Chemical identity, and three molecular weights

SNAP-8 is not the name the molecule is registered under. The FDA Global Substance Registration System files it as Acetyl Octapeptide-3 and types SNAP-8 on that record as a brand name rather than a chemical one. There is one such record: UNII 8K14HJF88S, CAS 868844-74-0 as the primary registry number, substance class protein, subunit sequence EEMQRRAD, and two terminal modifications recorded at complete extent, isoasparagine at the C-terminus and acetyl glutamic acid at the N-terminus. PubChem CID 76283482 carries the matching structure, formula C41H70N16O16S, molecular weight 1075.2, stereochemistry assigned at all eight centres, and 868844-74-0 among its synonyms; its systematic name terminates in 1-amino-3-carboxy-1-oxopropan-2-yl, which is the alpha-amide. The two records agree on the molecule.

Three different molecular weights circulate, and all three come from databases rather than from suppliers. The GSRS calculated-property field reads 1034.114 with formula C39H67N15O16S. That record encodes both terminal modifications explicitly, but the calculated weight is computed on the unmodified EEMQRRAD subunit and does not carry them. GSRS cross-links to PubChem CID 71587832, a record whose deposited structure contains an error: the carbonyl of the first peptide bond is drawn as a carbon-carbon double bond, which converts the N-terminal residue from 5-oxopentanoic acid to hex-5-enoic acid and yields formula C42H72N16O15S at 1073.2. A third record, CID 86080331, carries the correct formula with no stereochemistry assigned.

Average residue masses for EEMQRRAD sum to 1016.10. Adding a water molecule gives 1034.11, which is the GSRS number. Acetylation of the N-terminus adds 42.04 and amidation of the C-terminus subtracts 0.98, giving 1075.16, the PubChem number and the one printed on most specification sheets. Listings that write the sequence as Ac-EEMQRRAD-OH beside a weight of 1075.16 have paired a free-acid sequence with an amide weight; the acetylated free acid would be 1076.15, a difference of 0.99 daltons. Which of the two figures a page prints identifies the record it was copied from.

Where the sequence comes from

EEMQRRAD is a literal excerpt from human SNAP-25. Aligned against UniProt P60880, the eight residues occupy positions 12 to 19 of the 206-residue protein. Acetyl hexapeptide-8, the shorter peptide that preceded it commercially, is the same excerpt two residues shorter: EEMQRR, positions 12 to 17, carrying the same acetyl cap and terminal amide. The octapeptide adds the alanine and aspartate that follow in the parent sequence. Blanes-Mira and colleagues, publishing the hexapeptide in the International Journal of Cosmetic Science in 2002, framed the design rationale as competition with SNAP-25 for a position in the SNARE complex that drives calcium-dependent vesicle fusion.

The laboratory behind that work published two mechanism papers around it. In the Biochemical Journal in 2003, Blanes-Mira and colleagues screened an alpha-helix-constrained 17-mer combinatorial library of 137,180 sequences in positional-scanning format against reconstituted SDS-resistant SNARE core complex; deconvolution returned eight inhibitors, of which the most potent, acetyl-SAAEAFAKLYAEAFAKG-NH2, bore no relation to any SNARE sequence. The 2004 paper in the Journal of Neurochemistry mapped the SNAP-25 N-terminus and reported that the segment spanning Ala22 to Ile44 is essential for SNARE complex formation, with inhibitory potency correlating with propensity to adopt an alpha-helix.

Neither paper tested the octapeptide. The segment identified as essential in 2004 begins at residue 22, two residues past the end of EEMQRRAD, and the peptides that inhibited complex assembly in that work were patterned after 22 to 44 rather than 12 to 19. No assay of the octapeptide against the SNARE complex has been published by anyone. The peer-reviewed mechanistic mapping from the originating group covers residues 22 to 44, a different stretch of the protein from the one the two cosmetic peptides reproduce.

The published record on the octapeptide

A PubMed search for acetyl octapeptide-3, run on 18 August 2026, returns two records; the query is term-expanded rather than matched as a phrase. PubMed returns no records at all for SNAP-8, quoted or unquoted. Europe PMC returns eighteen for the INCI name and 158 for the brand string, the latter entirely string collisions across unrelated fields, among them remote sensing, neuroimaging, sleep medicine and dental materials. Inspecting the eighteen individually returns four human clinical studies whose formulations contain the ingredient, two of which surface only on full text. UniChem returns no ChEMBL entry for the compound, so no curated bioactivity record exists. In none of the four is acetyl octapeptide-3 the sole variable, and no animal or cell-culture study of it appears in any index.

Avcil and colleagues 2020, in the Journal of Cosmetic Dermatology, ran a monocentric twelve-week study of hyaluronic-acid microneedle patches loaded with arginine/lysine polypeptide, acetyl octapeptide-3, palmitoyl tripeptide-5, adenosine and seaweed extracts, applied at the outer corner of each eye and a defined area of the volar forearm. Reported instrumental changes were a 25.8% decrease in fine lines and wrinkles, a 15.4% improvement in hydration, and increases of 14.2% in dermal density and 12.9% in thickness. There was no control arm, and the retrieved abstract does not state how many subjects were enrolled.

Shin and colleagues 2024, in Annals of Dermatology, built a dissolving microneedle patch on a hyaluronic-acid backbone containing 0.03% SNAP-8, ascorbyl glucoside and sodium cyclic lysophosphatidic acid, applied overnight to one eye with a hyaluronic-acid-only placebo patch on the other. Twenty-four subjects enrolled and twenty-one completed. Within the treated eye, roughness parameter Ra fell from baseline at day 28 and Rz at days 7, 14 and 28, both at p below 0.01. Against the placebo patch on the contralateral eye, Ra and Rz differed at days 14 and 28 only, at p below 0.05. Three actives moved together in one patch; the design cannot separate their contributions, and the authors describe the combination as deliberate.

Two further human studies surface only on full-text search, both conducted by the manufacturer of the tested product. Moy and colleagues 2023, in the Journal of Cosmetic Dermatology, ran a twelve-week monadic study of a commercially available facial serum in women aged 35 to 55; thirty-three enrolled, thirty-one completed, subjects served as their own control, and acetyl octapeptide-3 was one item in a proprietary blend of neuropeptides, proteins, amino acids and marine extracts. Draelos and Diaz 2023, in Dermatology and Therapy, ran a twenty-four-week monadic study of a prototype serum in fifty women aged 35 to 65, forty-seven completing, in which the octapeptide sat alongside four other peptides, hyaluronic acid derivatives and antioxidants. Neither study carried a control arm, and neither isolates the peptide.

The wrinkle-depth percentages

The figures attached to this compound across vendor product pages, aggregator sites and ingredient directories are unusually specific: a maximum reduction in wrinkle depth of 63.13%, a mean of 34.98%, and 27.05% for acetyl hexapeptide-8 in the same comparison, after 28 days of twice-daily application at 10%. They recur across those pages down to the second decimal place, which indicates a single origin rather than independent replication. Several of the pages name that origin themselves: a technical dossier issued by the ingredient manufacturer, cited by title and not linked.

That dossier is not served publicly. A PubMed search returns nothing containing those values. A Europe PMC search on the INCI name and on the brand name returns no trial reporting them. A ClinicalTrials.gov intervention search across acetyl octapeptide-3 and SNAP-8 returns zero registered studies, while the same registry holds six for the hexapeptide, including a 70-participant Mahidol University study of a 10% gel on periorbital wrinkles that completed in September 2009 and never posted results. The octapeptide numbers are unverifiable in both directions: the protocol, the volunteer count, the blinding and the profilometry method cannot be inspected.

One octapeptide-specific wrinkle-depth result does appear in a PubMed-indexed journal, at second hand. Moy and colleagues 2023 report that a split-face in vivo study of a cream containing 3% of a 0.05% acetyl octapeptide-3 solution, applied twice daily for 28 days, lowered wrinkle depth by up to 38%, with an average decrease of 7.1%. The citation attached to that sentence is an ingredient manufacturer's product page rather than a journal, and no participant count, control arm or measurement method is given. Those figures do not match the 63.13% and 34.98% pair, and no source reconciles the two sets. What is on the record is a second-hand report of an unpublished study.

Published figures for the hexapeptide are more modest and traceable. Blanes-Mira 2002 reported wrinkle depth reduced up to 30% after 30 days from an oil-in-water emulsion containing 10% peptide in healthy women volunteers, without stating the number of volunteers in the abstract. Wang and colleagues 2013, in the American Journal of Clinical Dermatology, randomised 60 Chinese subjects to peptide or placebo in a 3:1 ratio, twice daily for four weeks on periorbital lines, and reported subjective total anti-wrinkle efficacy of 48.9% against 0% for placebo, with all silicone-replica roughness parameters decreased at p below 0.01.

Penetration was measured on the shorter peptide

Whether either peptide reaches a neuromuscular junction from a topical vehicle is unsettled, and every quantitative answer concerns the hexapeptide. Kraeling and colleagues, at the FDA Center for Food Safety and Applied Nutrition, applied a 10% oil-in-water emulsion of Ac-EEMQRR-amide at 2 mg per square centimetre to hairless guinea pig and human cadaver skin in diffusion cells for 24 hours, washed the surface, tape-stripped the stratum corneum with confocal verification, heat-separated epidermis from dermis, and quantified each fraction by hydrophilic interaction chromatography with tandem mass spectrometry against stable-isotope-labelled internal standards.

Most of the applied dose washed off. What remained stayed in the stratum corneum: 0.54% of the applied dose in guinea pig skin and 0.22% in human skin, declining with each successive strip. Epidermal recovery was 0.01% in both species. No peptide was detected in the dermis or in the receptor buffer beneath the skin, and no deacetylated metabolite appeared in any fraction. Hoppel and colleagues 2015, working on porcine ear skin with Franz-type cells and LC-MS/MS, found that a multiple water-in-oil-in-water emulsion significantly increased penetration over simple oil-in-water and water-in-oil vehicles, which places much of the variance in the vehicle rather than the peptide.

Zdrada-Nowak and colleagues reviewed this literature in the International Journal of Molecular Sciences in 2025 and recorded that the results conflict rather than converge: the 2002 paper described roughly 30% of the applied amount reaching receptor fluid within two hours, the FDA study found none after 24 hours. That review does not mention the octapeptide anywhere. No equivalent measurement has been published for it. It is the heavier molecule, 1075 daltons against 889, carrying the same two arginine residues, and the added aspartate contributes a further ionisable group.

Regulatory position and the route problem

Acetyl Octapeptide-3 appears in the European Commission cosmetic ingredient inventory with the declared functions humectant and skin conditioning. An inventory entry records a claimed function for labelling purposes; it is neither an efficacy finding nor a safety clearance at any particular concentration. No medicines regulator has approved the compound for any indication in any jurisdiction, and no marketing application for it appears in the public registries. The material is a cosmetic ingredient in law, and nothing more than that anywhere.

The Expert Panel for Cosmetic Ingredient Safety, which operates under the Cosmetic Ingredient Review programme, published an assessment of Acetyl Hexapeptide-8 Amide in the International Journal of Toxicology in August 2025. The panel concluded the hexapeptide safe in cosmetics at concentrations up to 0.005%, and that available data were insufficient to determine safety above that figure. The topical efficacy work cited here used 10% peptide (Blanes-Mira 2002; Kraeling 2015), roughly three orders of magnitude above 0.005%; the one microneedle study that reports a concentration used 0.03% (Shin 2024), roughly six times it. A search of the panel's published assessments returns no report on Acetyl Octapeptide-3 at all.

Everything published about this peptide concerns topical application or intradermal delivery by dissolving microneedle. Aggregator and forum pages nevertheless describe a lyophilised-powder format accompanied by reconstitution and injection instructions. No study at any level has administered acetyl octapeptide-3 by injection to an animal or a person. There is no pharmacokinetic measurement, no systemic toxicology, no immunogenicity assessment, and no published characterisation of residual counterion content in material distributed in that format.

What is not known

No study has tested acetyl octapeptide-3 as the sole variable in any system. All four human studies that contain it are multi-active formulations, none includes an arm in which the octapeptide is the only difference between test and control, and three of the four have no control arm at all, so nothing measured in any of them can be attributed to it. There is no animal study, no cell-culture assay, and no biochemical characterisation of the molecule against the SNARE complex, its nominal target: the mechanistic literature covers the hexapeptide and a different segment of SNAP-25, residues 22 to 44. Nothing has been published on skin penetration for this specific peptide, so whether it reaches the viable epidermis, let alone the dermis or a neuromuscular junction, is unmeasured. A ClinicalTrials.gov intervention search returns zero registered studies under either name. There is no pharmacokinetic data by any route, no systemic toxicology, no repeat-dose or chronic-exposure work, no reproductive or developmental assessment, no immunogenicity data, and no expert-panel safety assessment of the ingredient. The single octapeptide-specific wrinkle-depth figure that reaches a journal does so at second hand, citing a manufacturer product page, with no protocol, participant count or method attached.

Questions