Section 01
What it's used for
Wrinkle claims trace to marketing
The claim of 52% less wrinkling at 4% strength after 28 days traces only to the maker's marketing, not a study. Research so far: lab-dish tests and a 12-week trial mixing Syn-Ake with 4 actives (35-69% improvement) — none tested it alone.
▸Clinical wording
Syn-Ake (dipeptide diaminobutyroyl benzylamide diacetate) is promoted in vendor and community material for anti-wrinkle cosmetic use, but the widely repeated claim of 52% wrinkle reduction at 4% concentration after 28 days traces only to the ingredient manufacturer's marketing material, not to a peer-reviewed publication. Published literature is limited to an in vitro/in silico binding and antioxidant study with no clinical wrinkle data, and a multi-ingredient serum trial in which Syn-Ake was one of five actives and reported different results (35-69% wrinkle-score improvement over 12 weeks). No independent human trial isolating Syn-Ake's own effect on wrinkles was found.
Studied for expression lines
Syn-Ake is being studied as a cream or serum ingredient meant to reduce the small facial lines that form from repeated expressions, such as those around the eyes and forehead, by relaxing surface muscle activity where it is applied.
▸Clinical wording
Studied as a topical approach to reduce expression line formation.
Section 02
Mechanism of Action
Copied from a pit viper venom toxin
- SYN-AKE is a short synthetic peptide modelled on waglerin-1, a toxin from the temple pit viper.
- That toxin makes up roughly 17% of the venom's proteins and blocks nerve-to-muscle signalling.
- It competes with the natural transmitter acetylcholine for its site on the muscle receptor.
- In mouse nerve-muscle preparations it abolished adult muscle signals but left newborn tissue unaffected.
▸Clinical wording
Muscle-type nicotinic receptor antagonism inherited from waglerin-1
SYN-AKE (dipeptide diaminobutyroyl benzylamide diacetate) is a short synthetic peptide built around waglerin-1, a 24-residue proline-rich toxin that makes up roughly 17% of the venom proteins of the temple pit viper Tropidolaemus wagleri and converges functionally with three-finger alpha-neurotoxins on neuromuscular nicotinic receptors. Waglerin-1 acts as a competitive antagonist of the muscle-type nicotinic acetylcholine receptor, occupying the acetylcholine site on the postsynaptic side. In mouse nerve-muscle preparations it abolished end-plate potentials in adult wild-type animals and reduced acetylcholine responses with an IC50 near 50 nM, leaving neonatal preparations unaffected.
The toxin is fussy about its target
- The toxin binds one receptor interface about 2100-fold more tightly than the other in mice.
- Five specific amino acids on one receptor part account for most of that preference.
- Sensitivity appears only between days 11 and 12 after birth, when the adult part replaces the fetal one.
- Mouse receptors bind the toxin roughly 100-fold more tightly than rat or human receptors.
▸Clinical wording
Subunit and species dependence of the waglerin template
The block is not uniform across the adult receptor. Waglerin-1 binds the alpha-epsilon subunit interface of the mouse receptor about 2100-fold more tightly than the alpha-delta interface, and epsilon-subunit residues Gly-57, Asp-59, Tyr-111, Tyr-115 and Asp-173 account for most of that preference, with toxin residue Lys-34 pairing to Asp-173. This explains the developmental pattern: adult mice lacking the epsilon subunit resist the toxin, and end-plate sensitivity emerges only between postnatal days 11 and 12, when epsilon replaces the fetal gamma subunit. Species matters as much as subunit — mouse receptors bind waglerin-1 roughly 100-fold more tightly than rat or human receptors.
Little has actually been tested directly
- Published work on the synthetic cosmetic peptide is thin and never measured the nerve receptor.
- The single peer-reviewed study only simulated its binding to four proteins on a computer.
- The tightest and most stable simulated binding was to a longevity-linked enzyme, not a nerve receptor.
- Laboratory tests covered radical scavenging, cell toxicity and mutation risk, not nicotinic receptor activity.
▸Clinical wording
What has actually been measured for the cosmetic tripeptide
Published work on the synthetic peptide itself is thin and does not include receptor electrophysiology. The one peer-reviewed study docked SYN-AKE against MMP-1, MMP-8, MMP-13 and SIRT1 and ran 50-nanosecond molecular dynamics simulations; docking scores ordered MMP-13 below MMP-8 below MMP-1, and the lowest and most stable binding was to SIRT1 at -9.32 kcal/mol, with the peptide remaining in the active sites throughout the simulations. In vitro it showed concentration-dependent DPPH radical scavenging and was screened for cytotoxicity by MTT and for genotoxicity by the Ames test. These are computational and biochemical endpoints, not measurements at the nicotinic receptor.
Human tests used mixed products only
- The clinical record for skin use rests on finished cosmetic products, not on the isolated peptide.
- A serum combining three active ingredients raised elastic and collagen fibre markers in donated skin samples.
- Over 12 weeks clinical scores improved 35-69% for static wrinkles and 10-13% for dynamic wrinkles.
- Because three actives were applied together, the dipeptide's own share cannot be separated out.
▸Clinical wording
Human evidence comes from multi-ingredient formulations
The clinical record for topical use rests on finished cosmetic products rather than the isolated peptide. A serum combining acetyl hexapeptide-8, dipeptide diaminobutyroyl benzylamide diacetate and gluconolactone increased elastic- and collagen-fibre markers in ex vivo skin and, over 12 weeks, improved mean clinical scores for static wrinkles by 35-69% and for dynamic wrinkles by 10-13%, alongside gains in smoothness, radiance, pore appearance, elasticity and firmness. Because three actives were applied together, the share attributable to the dipeptide cannot be separated from that study design.
Section 03
Biological Pathways
- Waglerin-1 Template (nAChR Antagonism)SYN-AKE is built around waglerin-1, a viper-venom toxin that competitively blocks muscle-type nicotinic acetylcholine receptors, occupying the acetylcholine site and abolishing end-plate potentials in mouse muscle.
- Subunit and Species SelectivityWaglerin-1 binds the alpha-epsilon subunit interface about 2100-fold tighter than alpha-delta; sensitivity appears once epsilon replaces the fetal gamma subunit, and mouse receptors bind it far tighter than human.
- Docking Targets of the Synthetic TripeptideMolecular docking and dynamics simulations of the SYN-AKE tripeptide showed its most stable predicted binding to SIRT1, with weaker docking to MMP-1, MMP-8 and MMP-13; nAChR data are unreported for the peptide.
- Human Evidence from Combination SerumsA 12-week trial of a serum combining SYN-AKE with acetyl hexapeptide-8 and gluconolactone reduced static wrinkle scores by 35-69%, but the three-active formulation prevents attributing the effect to SYN-AKE alone.
Section 04
Dosage Information
Dipeptide diaminobutyroyl benzylamide diacetate (Waglerin-1 analog)| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Topical — manufacturer's own study | In-house study, 15 people per group | 4% in a cream, twice daily on the forehead for 28 days, volunteers aged 40–60: skin 21% smoother, wrinkles 15–20% shallower. | Never published in a peer-reviewed journal. The 52% quoted in marketing is one volunteer's best reading, not the group result. |
| Topical — placebo-controlled study | Double-blind study, two parallel groups | 29 people on SYN-AKE against 30 on placebo, women aged 40–55, twice daily on the face for 28 days: smoothing in 80%, wrinkles in 73%. | Supplier data again, with no peer-reviewed report to check the analysis against. Four weeks cannot show whether an effect lasts, fades or builds. |
| Topical — what the label % covers | Cosmetic labels and supplier use levels | Suppliers advise 1–4% of the trade material; 4% is the tested level. That material is glycerin and water, the dipeptide listed last. | So 4% on a label describes the glycerin solution, not the peptide. No supplier states the dipeptide content, so two 4% products need not match. |
| Topical — how much reaches muscle | The maker's argument for skin entry | Under 500 Da — below the usual size ceiling for passing through the outer skin layer. How much reaches muscle has never been measured. | Small enough to cross is not proof of crossing. The receptor it should block sits below the skin, where nerve meets muscle, and nothing shows it arrives. |
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
Supplied within a finished cosmetic formulation and kept at room temperature; the product is described as stable under normal storage and compatible with standard cosmetic ingredients and vehicles.
After opening
A precise use-by period after opening is not specified and depends on the individual product and its packaging; the formulation is designed to remain stable under typical cosmetic storage conditions.
Section 07
Side Effects & Precautions
Well-tolerated topically. No systemic absorption at cosmetic concentrations. Rare mild skin irritation.
Section 08
Regulatory Status
It is marketed on a muscle-relaxing effect borrowed from snake venom research, but as a topical peptide it is regulated the same way as any other cosmetic active — through safety documentation, not drug approval.
FDA / United States
Cosmetic ingredient, no pre-market approval
Dipeptide Diaminobutyroyl Benzylamide Diacetate is regulated under the FD&C Act as a cosmetic and is not reviewed by FDA before sale. No CIR safety assessment specific to this peptide was found; its safety data comes from supplier and industry testing rather than an independent expert panel.
EU
Listed in the CosIng database
The European Commission lists it as a skin-conditioning agent under Regulation (EC) 1223/2009; it is not on the restricted-substances annexes, so no SCCS opinion has been published for it specifically.
Claims boundary
Wording, not the peptide, decides the category
Syn-Ake is sold on the claim that it inhibits micro-contractions the way the temple viper peptide waglerin-1 does. FDA has warned companies over claims that a product "reduces wrinkle depth by attenuating muscle contraction" — language that describes changing the skin's structure and risks drug classification.
WADA
Not on the Prohibited List
Dipeptide Diaminobutyroyl Benzylamide Diacetate is not a peptide hormone or growth factor, so it falls outside category S2 and carries no sport-specific restriction for competing athletes.
This status covers Syn-Ake as a topical cosmetic ingredient used within labelled limits; claims describing a drug-like effect — changing skin structure, treating a condition — move a product into drug regulation regardless of the label. Regulatory status differs between jurisdictions and can change — check the current rules of your own regulator.
Section 09
Research Studies
- [1]Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptorMcArdle JJ, Lentz TL, Witzemann V, Schwarz H, Weinstein SA, Schmidt JJ · The Journal of Pharmacology and Experimental Therapeutics · 1999
- [2]Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of waglerin-1 for nicotinic acetylcholine receptorsMolles BE, Rezai P, Kline EF, McArdle JJ, Sine SM, Taylor P · Journal of Biological Chemistry · 2002
- [3]Residues in the epsilon subunit of the nicotinic acetylcholine receptor interact to confer selectivity of waglerin-1 for the alpha-epsilon subunit interface siteMolles BE, Tsigelny I, Nguyen PD, Gao SX, Sine SM, Taylor P · Biochemistry · 2002
- [4]De novo assembly of venom gland transcriptome of Tropidolaemus wagleri (temple pit viper, Malaysia) and insights into the origin of its major toxin, waglerinTan CH, Tan KY, Tan NH · Toxins · 2023
- [5]Anti-aging activity of Syn-Ake peptide by in silico approaches and in vitro testsGok B, Budama-Kilinc Y, Kecel-Gunduz S · Journal of Biomolecular Structure and Dynamics · 2024
- [6]The effect of a serum containing acetyl hexapeptide-8, dipeptide diaminobutyroyl benzylamide diacetate and gluconolactone on skin biomarkers, wrinkles and skin texture: ex vivo and clinical studiesZhu M, He X, Zhu Z, Lynch S, Wang H, Zhou X, Tu Y, Steel A, Hsu KC, Niu Y, Cho A, Hashimoto M, Yan X, Su M, Wang W · International Journal of Cosmetic Science · 2026
Section 10
Frequently Asked Questions
The widely repeated claim of 52% wrinkle reduction after 28 days traces only to the ingredient manufacturer's own marketing material, not to a peer-reviewed study, and even that source describes 52% as one volunteer's best result rather than the group average. The only peer-reviewed publication on Syn-Ake itself is a computational and in vitro study — molecular docking plus an antioxidant assay — with no clinical wrinkle data at all.
Its designed mechanism is genuinely different from Botox: it mimics waglerin-1, a viper-venom peptide that blocks the receptor on the muscle side of the neuromuscular junction, rather than blocking nerve signal release the way Botox does. But whether a topically applied peptide actually reaches that receptor, buried beneath the skin at the nerve-muscle junction, has never been measured — its small size, under 500 Da, only means it is theoretically able to cross the outer skin layer.
Suppliers sell Syn-Ake pre-diluted in a glycerin-and-water carrier and advise formulators to use that material at 1–4% of a finished product, with 4% being the concentration used in the manufacturer's own testing. The peptide itself is listed last among the carrier's ingredients and its exact content is not disclosed, so two products both labelled 4% Syn-Ake do not necessarily contain the same amount of actual peptide.
The one peer-reviewed study screened it for cytotoxicity and genotoxicity in lab assays and found no red flags. At the concentrations used in finished cosmetics it is described as well tolerated with no systemic absorption, and reported side effects are limited to rare, mild skin irritation.
It is a synthetic tripeptide (INCI name dipeptide diaminobutyroyl benzylamide diacetate) engineered to mimic waglerin-1, a toxin that makes up about 17% of the venom proteins of the temple pit viper. The synthetic version reproduces the toxin's receptor-blocking idea in a small, stable cosmetic ingredient rather than using venom itself.