Syn-Ake

A synthetic cosmetic peptidomimetic (INCI: dipeptide diaminobutyroyl benzylamide diacetate) designed to imitate waglerin-1 from temple viper venom, marketed for topical expression-line smoothing on a manufacturer-described mechanism of reversible antagonism at the muscle nicotinic acetylcholine receptor.

Also referenced as: Dipeptide Diaminobutyroyl Benzylamide Diacetate, SYN-AKE, Syn-Ake peptide, beta-Alanyl-L-prolyl-2,4-diamino-N-(phenylmethyl)butanamide

Also appears in: Longevity

What is Syn-Ake?

Syn-Ake is a trade name developed at Pentapharm (Basel) and now carried by DSM-Firmenich, for a small synthetic peptidomimetic whose INCI name is dipeptide diaminobutyroyl benzylamide diacetate. Structurally it is β-alanyl-L-prolyl-2,4-diamino-N-(phenylmethyl)butanamide supplied as a bis-acetate salt — three residues (β-alanine, L-proline, and 2,4-diaminobutyric acid) capped at the C-terminus as a benzylamide, CAS 823202-99-9, C₂₃H₃₇N₅O₇, molecular weight about 495.6 for the diacetate (PubChem CID 71465152). It is peptide-derived rather than a true peptide sequence: two of its three residues — β-alanine and 2,4-diaminobutyric acid — are non-proteinogenic, and the C-terminal cap is a benzyl group, not an amino acid.

The molecule was designed as a small-molecule imitation of waglerin-1, a 22-amino-acid lethal peptide from the venom of the temple pit viper Tropidolaemus wagleri (formerly Trimeresurus wagleri). It reaches the research-peptide market on the strength of its cosmetic positioning as a topical alternative to botulinum toxin for expression lines, and it is typically sold as a topical-only compound alongside other cosmetic peptides such as Argireline and SNAP-8.

How it works

• The template toxin is a competitive muscle-nAChR antagonist. Waglerin-1 is a 22-amino-acid competitive antagonist of the muscle nicotinic acetylcholine receptor that binds roughly 2,100-fold more tightly to the α–ε than to the α–δ binding-site interface of the mouse receptor (Molles et al., Journal of Biological Chemistry, 2002;277(7):5433–5440).
• Its selectivity is for the adult endplate receptor. Waglerin-1 blocks the mature ε-subunit-containing receptor specifically: neonatal mice and adult ε-subunit knockout mice resist it, while adult wild-type endplate responses to acetylcholine are suppressed with an IC₅₀ near 50 nM (McArdle et al., Journal of Pharmacology and Experimental Therapeutics, 1999;289(1):543–550). Blocking that receptor relaxes muscle, and the cosmetic rationale is that less contraction in facial mimetic muscle means shallower expression lines.
• Potency is species-dependent. Non-conserved residues at the binding site — ε-subunit positions 59 and 115, plus α-subunit residues 187 and 189 — govern affinity, and waglerin-1 binds the human α–ε interface about 100-fold less tightly than the mouse one (Molles et al., Journal of Biological Chemistry, 2002; further mapped in Molles et al., Biochemistry, 2002;41(25):7895–7906).
• The receptor-level claim for Syn-Ake itself is manufacturer-supplied. DSM-Firmenich describes the ingredient as a reversible antagonist at the muscular nicotinic acetylcholine receptor: the receptor is blocked, the ion channel stays closed, sodium is not taken up, and the muscle cell stays relaxed. The only supporting data the manufacturer publishes is a functional assay in which 0.5 mM peptide progressively reduced the contraction frequency of innervated muscle cells (−36% at one minute, −67% at two hours, −82% at two days), with the effect described as reversible — a test concentration roughly four orders of magnitude above the 50 nM at which waglerin-1 blocks the endplate response, and the company’s own literature states that Syn-Ake’s activity is attenuated relative to waglerin-1. None of that is peer-reviewed, and the single PubMed-indexed study of the molecule does not test nicotinic receptors at all: it docks the compound against matrix metalloproteinases and SIRT1 and measures radical scavenging, cytotoxicity, and genotoxicity (Gok et al., Journal of Biomolecular Structure and Dynamics, 2024;42(10):5015–5029).

Research status

The published record on this compound is thin, and it is much thinner than the record on the venom peptide it imitates.

No registered trials, and almost no dedicated literature. ClinicalTrials.gov returns zero studies for Syn-Ake, for waglerin, and for diaminobutyroyl-containing interventions. PubMed indexes exactly two records naming the compound — one under the trade name, one under the INCI name — against 29 records for “waglerin”.

Study 1 — mechanism-agnostic lab work. Gok et al., Journal of Biomolecular Structure and Dynamics, 2024;42(10):5015–5029 ran molecular docking and 50-ns molecular-dynamics simulations of Syn-Ake against MMP-1, MMP-8, MMP-13 and SIRT1 (best predicted binding to SIRT1 at −9.32 kcal/mol), plus DPPH radical-scavenging, MTT cytotoxicity, and Ames genotoxicity assays. It is in silico and in vitro only, involves no human subjects, and — notably for a molecule sold on a neuromuscular story — contains no nicotinic-receptor assay.

Study 2 — a clinical result that cannot be attributed to this ingredient. Zhu et al., International Journal of Cosmetic Science, 2026 (online ahead of print, doi 10.1111/ics.70087), a study run by L’Oréal research centers, tested a serum containing acetyl hexapeptide-8, dipeptide diaminobutyroyl benzylamide diacetate, gluconolactone, niacinamide, and laminaria extract. One ex vivo arm measured MMP-1, elastic fibers and collagen types I, III, IV and XVII; clinical study 1 (n = 50) assessed static wrinkles and skin quality, and clinical study 2 (n = 42) assessed dynamic wrinkles. Static-wrinkle clinical scoring improved 35% to 69% across wrinkle types at 12 weeks and dynamic-wrinkle scoring by 10% to 13% (all p < 0.001). Because five actives were present in one formula, the design cannot isolate any contribution from Syn-Ake.

The widely repeated efficacy figures are manufacturer literature, and they do not say what product copy says they say. The Pentapharm/DSM technical brochure describes a 28-day in vivo test of a 4% preparation against placebo, applied to the forehead twice daily, in 15 volunteers per group aged 40–60 — not the 100-volunteer design sometimes attached to this number, which belongs to a separate DSM “Mothers & Daughters” study (25 per group) about delaying the onset of wrinkles. The brochure’s own charted results are roughness reductions of 21% (Ra), 20% (Rz) and 15% (Rt); its headline is “up to 52% reduction in the appearance of wrinkle size”, a best-case figure that product copy routinely restates as a flat “52% wrinkle-depth reduction in 28 days”. None of it is peer-reviewed, and no independent group has replicated it.

The venom peptide is far better characterized than the cosmetic mimic. The two lethal peptides later named waglerins were isolated and sequenced from T. wagleri venom, with a murine intraperitoneal LD₅₀ of 0.369 mg/kg for lethal peptide I (Weinstein et al., Toxicon, 1991;29(2):227–236). Structure-function work showed the single intramolecular disulfide bond and at least one of the first five residues are required for lethality (Schmidt & Weinstein, Toxicon, 1995;33(8):1043–1049), and venomics found six waglerin forms making up 38.2% of total venom protein (Tan et al., Scientific Reports, 2017;7:43237). None of this work involves Syn-Ake.

There is no published human pharmacokinetic data, no skin-penetration study, and no independent receptor-binding measurement for the cosmetic molecule. No regulatory authority has approved it as a drug for any indication.

Common dosage forms

• Trade-material solution for formulators, supplied as a preservative-free glycerin-based aqueous solution (INCI on the label: glycerin, aqua, dipeptide diaminobutyroyl benzylamide diacetate). The manufacturer suggests using it at 1–4% of a finished formula and ran its own in vivo test at 4%. How much peptide that solution contains is not disclosed in the manufacturer’s literature, so the peptide concentration of a finished cream is not publicly documented — the “4%” in marketing copy refers to the trade solution, not to the peptide.
• Finished cosmetics — serums, creams and eye creams, commonly blended with other “expression line” peptides such as acetyl hexapeptide-8 (Argireline), pentapeptide-18 (Leuphasyl) or pentapeptide-3 (Vialox), which makes single-ingredient attribution difficult on a label.
• Research-market presentations — lyophilized powder in vials, often around 200 mg, and pre-mixed topical solutions, generally labeled topical-only.
• There is no injectable or oral precedent in the published record. Topical application is the only route with any human data behind it.

This section describes formats only and is not dosing guidance.

Key considerations

• Regulatory status is cosmetic, not therapeutic. Dipeptide diaminobutyroyl benzylamide diacetate is a cosmetic ingredient that has never been through FDA drug review, and cosmetics do not require FDA approval before marketing. Under FDA’s framework, a product intended simply to make lines less noticeable is a cosmetic, but claims to remove wrinkles or otherwise affect the structure or function of the body push a product into drug territory — which is exactly the line that “muscle relaxing” and “alternative to botulinum toxin” language walks, and the manufacturer’s own brochure uses that framing.
• The mechanism has a delivery gap nobody has published across. Waglerin-1’s target is the ε-containing nicotinic receptor at the neuromuscular junction, which sits beneath the epidermis and dermis. Skin does carry its own non-neuronal cholinergic system, with keratinocytes expressing nicotinic receptors (Kurzen et al., Hormone and Metabolic Research, 2007;39(2):125–135), but those are not the adult endplate receptor the venom peptide blocks. No published study shows how much intact Syn-Ake reaches facial mimetic muscle after topical application.
• Animal potency does not transfer cleanly to humans. Even for waglerin-1 itself, affinity at the human α–ε interface is roughly 100-fold lower than at the mouse interface (Molles et al., 2002). Any potency intuition borrowed from rodent neuromuscular work overstates the human case before the weaker synthetic analog is even considered.
• “Snake venom peptide” marketing blurs an important distinction. The parent toxin is lethal in mice and also inhibits GABA-A current in nucleus accumbens neurons freshly isolated from 3- to 7-day-old rats, with an IC₅₀ of 2.5 µM against current evoked by 10 µM GABA (Ye et al., Brain Research, 1999;837(1-2):29–37). Syn-Ake is a much smaller, much weaker synthetic analog and contains no venom-derived material — but it also has none of that toxin’s characterization behind it. In vitro work reported a safe concentration range on cytotoxicity and Ames testing (Gok et al., 2024); there is no published safety data for any non-topical route.
• Naming is genuinely confusing. “Syn-Ake” is a Pentapharm/DSM-Firmenich trademark, not a chemical name; research listings that use it are generic material of varying provenance. The INCI name says “dipeptide” because it treats β-alanyl-proline as the peptide core and names the diaminobutyroyl benzylamide as a modification of it — the assembled molecule still carries three residues, which is why the manufacturer’s own brochure calls it a synthetic tripeptide. Describing it as a tripeptide is therefore fair; labeling it “Tripeptide-3” is not, because that INCI name belongs to a different ingredient, the alanyl-histidyl-lysine peptide better known as AHK. It is also not waglerin-1, which is a 22-residue disulfide-containing venom peptide available only as a research toxin.
• The evidence base is two papers deep. One is computational and in vitro with no receptor assay; the other tests a five-active formula. Everything else supporting the compound is manufacturer literature or extrapolation from a different molecule.