SYN-AKE

Overview

SYN-AKE (INCI: Dipeptide Diaminobutyroyl Benzylamide Diacetate; CAS 823202-99-9; also referred to as tripeptide-3) is a synthetic peptide cosmetic ingredient. DSM-Firmenich describes it as a small synthetic peptide that helps reduce the appearance of wrinkles and laughter lines while allowing the face to relax without losing the ability to make expressions^2,4. peptideinsight.com states it was developed by Pentapharm (now part of DSM) as a cosmeceutical anti-wrinkle ingredient inspired by the neurotoxic mechanism of snake venom, and that it is not regulated as a drug but marketed as a cosmetic ingredient(vendor claim). DSM notes it received the 2006 Swiss Technology Award², and cenexalabs.com describes it as first developed in Switzerland in 2006.

The Waglerin-1 Template

Vendor and reference sources describe SYN-AKE as mimicking Waglerin-1, a peptide found in the venom of the Temple Viper (Tropidolaemus wagleri)^2,3. peptideinsight.com describes Waglerin-1 as a 22-amino-acid disulfide-containing peptide toxin of approximately 2.6 kDa that produces neuromuscular paralysis through selective post-synaptic blockade of the nicotinic acetylcholine receptor, selective for the epsilon-subunit-containing adult muscle nAChR (IC50 ~300 nM) while sparing the gamma-subunit fetal form(vendor claim). Sources disagree on the native peptide's length — most describe Waglerin-1 as 22 amino acids, while biotechpeptides states it is 21 amino acids.

A contested identity. Sources disagree on what SYN-AKE actually is. DSM material, peptahub, pepguide and seekpeptides describe it as a synthetic tripeptide with a molecular weight below 500 Da (~439.5 g/mol)². By contrast, peptidings.com characterizes it as a dipeptide derivative of ~390 Da, structurally nothing like the 22-amino-acid Waglerin-1 it claims to mimic, and kalios.health describes it as a dipeptide supplied as the diacetate salt (503 Da diacetate salt / 432 Da free base)(vendor claim). The INCI name itself — Dipeptide Diaminobutyroyl Benzylamide Diacetate — indicates a dipeptide.

Reported Mechanism

In vitro, SYN-AKE is described as a reversible competitive antagonist at the muscular nicotinic acetylcholine receptor. Vendor material states the reversible blockade keeps the ion channel closed, prevents Na+ uptake, keeps muscle cells relaxed, and inhibits nerve-impulse transmission to relax facial muscles². peptahub.com contrasts it with Argireline-class peptides that target the SNARE complex, describing SYN-AKE instead as competing for the acetylcholine binding site and reducing signal-transduction efficiency without fully blocking it, and pepguide.io calls it the only cosmetic peptide that directly targets the receptor rather than the neurotransmitter-release machinery(vendor claim).

A separate PubMed-indexed in silico/in vitro study reports the Syn-Ake peptide interacts with matrix metalloproteinases (MMPs) and Sirtuin 1 (SIRT1), with docking scores ordering MMP-13 < MMP-8 < MMP-1 and the lowest, most stable SIRT1 binding at -9.32 kcal/mol; the peptide remained stable in the active sites of MMP-13 and SIRT1 across 50 ns molecular dynamics simulations and showed concentration-dependent DPPH radical scavenging (antioxidant) activity¹. These MMP/SIRT1 and antioxidant findings come from a single computational/lab study and are not clinical.

Reported Evidence

• In vitro contraction assays: peptahub.com reports up to 80% reduction in muscle contraction signaling at effective concentrations; pepguide.io reports up to 82% reduction in contraction frequency at optimal concentrations and states in vitro binding studies confirmed selectivity for the muscular-type nAChR over neuronal subtypes(vendor claim). omizzur.com states 0.025% of the snake-venom-like tripeptide reduced muscle contraction rate by 36% after one minute and 82% after two hours in cultured muscle cells(vendor claim).
• Manufacturer-sponsored human studies: A DSM manufacturer-sponsored study applied a cream twice daily for 4 weeks in a total of 100 volunteers (25 per group), comparing SYN-AKE 4% against placebo and measuring smoothing (Ra) and anti-wrinkle effects (Rz, Rt) on crow's feet after 28 days, reporting visibly reduced wrinkle depth². DSM also describes visible deep-wrinkle smoothing after 4 weeks and an 'age-freezing' effect delaying wrinkle appearance when used earlier in life². pepguide.io attributes a double-blind, placebo-controlled study to Lintner et al. (2009) reporting significant crow's-feet wrinkle depth reduction, with DSM documentation reporting mean reductions of 52% after 28 days(vendor claim).
• The disputed 52% figure: Multiple vendor profiles cite a 52% wrinkle depth reduction after 28 days at 4%(vendor claim). However, kalios.health states this number traces only to a Pentapharm supplier brochure reproduced in trade press rather than a peer-reviewed study, and peptidings.com states there is not a single peer-reviewed clinical trial testing Syn-Ake in humans, that the one manufacturer study (45 people, 28 days) was never published in a medical journal, never independently replicated, and its methods remain unknown(vendor claim). Sources also disagree on trial size: DSM describes 100 volunteers total², peptidings reports 45 people, and omizzur references a fifty-subject assay.

Key Limitations

Multiple sources note that independent academic validation is limited, that all published human evidence traces to the manufacturer or ingredient suppliers, and that no independent RCTs exist as of 2026. peptidings.com states no published lab study confirms that Syn-Ake actually blocks the nerve receptors it claims to target, and no penetration data show it reaching facial muscles several millimeters below the skin surface(vendor claim). cenexalabs.com states it has not been studied via injection routes and that comprehensive trials on long-term safety, optimal dosing, and mechanism validation remain limited(vendor claim). Some vendor claims involve unrelated compounds — peptideinitiative's botulinum-complement example actually describes a serum containing acetyl hexapeptide-8 rather than Syn-Ake, and naturalorganicskincare adds a general collagen-production mechanism not supported by the primary neuromuscular mechanism described elsewhere.

Safety & Tolerability

This is a topical cosmetic ingredient, not an injectable drug. cenexalabs.com states Syn-AKE has not been studied via injection routes(vendor claim).

• peptahub.com describes the effect as fully reversible and non-paralytic, and notes reported side effects of mild tingling at the application site and rare redness(vendor claim). pepguide.io states clinical studies report no irritation, sensitization, or systemic neuromuscular effects at recommended concentrations, no tachyphylaxis or tolerance with extended use, and a fully reversible effect(vendor claim).
• peptideinitiative.com states SYN-AKE demonstrates excellent topical tolerability with no serious adverse events reported in cosmetic use spanning 15+ years, with occasional mild tingling or slight dryness as expected local skin responses, and negligible systemic absorption(vendor claim).
• The PubMed-indexed in silico/in vitro study reports Syn-Ake showed a high efficacy and safety profile in in silico and in vitro analyses, with a safe dose determined, cytotoxicity assessed via MTT test, and genotoxicity via Ames test¹.

Regulatory Status

peptahub.com states SYN-AKE is approved as an OTC cosmetic ingredient in the EU and US(vendor claim). kalios.health states it is listed in the European Cosmetic Ingredients Database (CosIng) without restriction and is permitted as a leave-on cosmetic ingredient in essentially every regulated cosmetic market globally(vendor claim). peptideinsight.com notes it is not regulated as a drug but marketed as a cosmetic ingredient(vendor claim).

Important Caveats

Safety statements above derive largely from manufacturer/supplier and vendor sources. Multiple sources note there are no independent RCTs as of 2026, that comprehensive long-term safety trials remain limited, and that the underlying mechanism and skin penetration to the neuromuscular junction remain unproven. kalios.health notes that while the native venom peptide Waglerin-1 has well-characterized toxicology, Syn-Ake itself has no peer-reviewed randomized trial in the cosmetic indication(vendor claim).

Dosing & Formulation

No dose has been established for this compound as a drug. SYN-AKE is marketed as a topical cosmetic ingredient, not a regulated drug, and it has not been studied via injection routes. The figures below are what sources report for cosmetic formulation — not medical guidance.

Supplied raw material (DSM formulation guidelines⁴)

• The raw material contains 0.1–1% active ingredient (Dipeptide Diaminobutyroyl Benzylamide Diacetate), Glycerin >50%, and Aqua 25–50%.
• pH 4.5–5.5 as supplied.
• Recommended use level: 1–4% SYN-AKE for skin-care preparations.
• Final formulation pH range: 3.0–7.5; compatible with up to 50% ethanol.

seekpeptides.com and pepguide.io similarly note the material consists of glycerin, water, and the active dipeptide, with the diacetate salt reported at 503 Da and the free base at 432 Da by kalios.health (CAS 823202-99-9)(vendor claim). kalios.health also states it is supplied as a water-soluble white powder typically diluted to 0.05–0.1% active in a glycerin/water carrier(vendor claim).

Reported use concentrations

• kalios.health: used cosmetically worldwide at 1–4% in leave-on serums and eye creams; pulse.co.ke: typically 1–4% in products³; peptidings.com: typical formulation concentrations of 1–4%.
• peptahub.com: typical use is 4% in a finished serum applied twice daily to forehead, crow's feet, and perioral areas(vendor claim).
• seekpeptides.com: effective concentrations of 1–5%, with 4% described as optimal (lower 1–2% for prevention, higher 4–5% for existing wrinkles)(vendor claim).
• omizzur.com: a minimum addition amount of 0.01% in products(vendor claim).
• peptideinitiative.com: applied topically to clean, dry skin, not affected by food intake(vendor claim).

Handling & stability

DSM formulation guidelines describe SYN-AKE as fast acting and long lasting with a fully reversible effect, miscible with water, insoluble in lipophilic components, processable up to 2 hours at 70°C, and compatible with emulsifiers, emollients, waxes, preservatives, hydrocolloids, sunscreens, and detergents⁴. omizzur.com advises storage in a sealed container away from light and humidity at 15–25°C, and notes it can be heat-treated at 70°C for less than 2 hours or cold-treated⁴. seekpeptides.com states it tolerates room-temperature storage in sealed containers, while peptideinitiative.com advises that once reconstituted it should be kept refrigerated at 36–46°F (2–8°C) and used within the labeled timeframe, typically 14–28 days(vendor claim).

Reported timeline of effect

seekpeptides.com states clinical studies show 52% wrinkle depth reduction after 28 days, with visible improvements appearing within 5–7 days and peak effects at 28 days; naturalorganicskincare.com states full effects take about 30 days(vendor claim). As noted in the safety and overview sections, the 52% figure and the underlying study are disputed — kalios.health attributes the number to a supplier brochure rather than a peer-reviewed study, and peptidings.com states the sole manufacturer study was never published, replicated, or its methods disclosed(vendor claim).

1. 1.
   Anti-aging activity of Syn-Ake peptide by in silico approaches and in vitro tests(opens in a new tab)

   Tier 2Web · pubmed.ncbi.nlm.nih.gov
2. 2.
   SYN-AKE®(opens in a new tab)

   Tier 2Web · dsm-firmenich.com
3. 3.
   How does Syn-AKE Peptide work? | Pulse Kenya(opens in a new tab)

   Tier 3Web · pulse.co.ke
4. 4.
   SYN®-AKE(opens in a new tab)

   Tier 4Web · dsm.com