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SYN-AKE

Tier 3 · Reported use
Also known as Dipeptide diaminobutyroyl benzylamide diacetate · Waglerin-1 analogue

The strongest evidence is Tier 2 (in vitro / in silico mechanistic work). In vitro assays report reduced muscle contraction signaling and nAChR antagonism, and a single PubMed-indexed in silico/in vitro study reports MMP/SIRT1 interactions and DPPH antioxidant activity. Human evidence is limited to manufacturer-sponsored observational cosmetic studies (the disputed '52% wrinkle reduction' figure); multiple sources note no independent peer-reviewed human RCTs exist as of 2026 and that skin penetration to the neuromuscular junction is unproven. Sources also disagree on basic facts such as whether the molecule is a dipeptide or tripeptide and its molecular weight.

Half-life
Not recorded
Routes
Topical
Goals
Cosmetic anti-aging / anti-wrinkle · Skin appearance / expression-line reduction
Cost / mg
Not recorded

How it works

Vendor and reference sources describe SYN-AKE as a small synthetic peptide designed to mimic Waglerin-1, a component of Temple Viper venom, in order to relax facial muscles and soften the appearance of expression wrinkles while still allowing normal expressions. According to these sources, it works by acting like a reversible plug at the receptor on muscle cells that normally receives the nerve signal to contract, so muscle cells stay more relaxed and expression lines are less deepened. DSM-Firmenich describes it as reducing the appearance of wrinkles and laughter lines. Multiple sources caution that independent validation is limited and that it is unproven whether a topically applied peptide actually reaches facial muscles millimeters below the skin.

Overview

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 (src-1, src-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 (src-2, src-6, src-11). DSM notes it received the 2006 Swiss Technology Award (src-1), and cenexalabs.com describes it as first developed in Switzerland in 2006 (src-10).

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) (src-1, src-2, src-6, src-7, src-12, src-13). 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 (src-2, src-8). Sources disagree on the native peptide's length — most describe Waglerin-1 as 22 amino acids (src-2, src-3, src-8), while biotechpeptides states it is 21 amino acids (src-14).

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) (src-1, src-2, src-6, src-7, src-11). 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 (src-3), and kalios.health describes it as a dipeptide supplied as the diacetate salt (503 Da diacetate salt / 432 Da free base) (src-8). 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 muscles (src-1, src-6, src-11, src-13). 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 (src-6, src-7), and pepguide.io calls it the only cosmetic peptide that directly targets the receptor rather than the neurotransmitter-release machinery (src-7).

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) activity (src-5, src-9). 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 (src-6); 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 (src-7). 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 (src-13).
  • 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 depth (src-1). DSM also describes visible deep-wrinkle smoothing after 4 weeks and an 'age-freezing' effect delaying wrinkle appearance when used earlier in life (src-1). 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 (src-7).
  • The disputed 52% figure: Multiple vendor profiles cite a 52% wrinkle depth reduction after 28 days at 4% (src-2, src-7, src-11, src-14). However, kalios.health states this number traces only to a Pentapharm supplier brochure reproduced in trade press rather than a peer-reviewed study (src-8), 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 (src-3). Sources also disagree on trial size: DSM describes 100 volunteers total (src-1), peptidings reports 45 people (src-3), and omizzur references a fifty-subject assay (src-13).

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 (src-2, src-3, src-6, src-8, src-10). 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 (src-3, src-13). 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 (src-10). Some vendor claims involve unrelated compounds — peptideinitiative's botulinum-complement example actually describes a serum containing acetyl hexapeptide-8 rather than Syn-Ake (src-9), and naturalorganicskincare adds a general collagen-production mechanism not supported by the primary neuromuscular mechanism described elsewhere (src-16).

What the research shows

165 findings extracted from the 16 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 2 human trial findings, 6 human study findings, 3 animal findings, 3 in vitro findings, 8 expert opinion findings, 8 anecdotal findings and 1 theoretical finding.

  • human trialLintner et al. (2009) reported that profilometric analysis demonstrated significant wrinkle depth reduction in the crow's feet area, with some subjects showing improvements within the first week of application.3

  • human trialDSM's clinical documentation reports mean wrinkle depth reductions of 52% after 28 days of twice-daily application.3

  • human studyVisible deep wrinkle smoothing after only 4 weeks4

  • human studyWhen used earlier in time, SYN-AKE helps delaying the appearance of wrinkles, with age-freezing effects4

  • human studyMeasurement of the smoothing (Ra) and anti-wrinkle effect (Rz and Rt) of SYN-AKE (4%) measured on the crow's feet after 28 days showed visibly reduced wrinkle depth4

  • human studyA 28-day manufacturer-sponsored clinical trial reported reduction in wrinkle depth and skin smoothness improvements observable by digital imaging5

  • human studyClinical studies show 52% wrinkle depth reduction after 28 days of consistent use9

  • human studyReal-world clinical experience demonstrated a topical neuro-peptide serum containing acetyl hexapeptide-8 complemented botulinum toxin injections, improving radiance and reducing fine lines11

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  • animalSyn-AKE studies indicate that the peptide may reduce the number of muscular movements and reduce cellular mobility2

  • animalIn a quarter-year research initiative involving models exhibiting mild to moderate wrinkling in the stratum corneum, Syn-AKE may exhibit both immediate and sustained impacts on skin topography2

  • animalFurther study highlighted the potential of Syn-AKE which possibly led to as much as a 52% reduction in wrinkle visibility2

  • in vitroIn muscle cell contraction assays, SYN-AKE reduced contraction frequency by up to 82% at optimal concentrations.3

  • in vitroIn vitro studies showed up to 80% reduction in muscle contraction signaling at effective concentrations5

  • in vitroUsing 0.025% snake venom like tripeptide can reduce muscle contraction rate by 36% after one minute and 82% after two hours in cultured muscle cells8

  • expert opinionApitegromab is positioned as the most clinically advanced selective myostatin inhibitor currently in development with active Phase 3 program and FDA Fast Track designation7

  • expert opinionAfamelanotide (Scenesse) is the FDA-approved pharmaceutical formulation with proven safety and efficacy from Phase 3 clinical trials7

  • expert opinionSYN-AKE is among the fastest-acting cosmetic peptides for wrinkle reduction11

  • expert opinionSyn-AKE has been studied extensively in in vitro systems and limited human topical application trials12

  • expert opinionThere is not a single peer-reviewed clinical trial testing Syn-Ake in humans13

  • expert opinionThe one manufacturer study (45 people, 28 days) was never published in a medical journal, never independently replicated, and its methods remain unknown13

  • expert opinionNo published lab study confirms that Syn-Ake actually blocks the nerve receptors it claims to target13

  • expert opinionSyn-Ake has no peer-reviewed randomized trial in cosmetic indication14

  • anecdotalSYN-AKE peptide can reduce the generation of wrinkles by inhibiting muscle contraction8

  • anecdotalSYN-AKE Peptide could significantly reduce the expression lines on the forehead8

  • anecdotalThe activity of snake venom like tripeptide was significantly higher than that of acetyl hexapeptide-88

  • anecdotalStudies have shown that using Syn-Ake for four weeks and twice a day can smooth the look of wrinkles by more than 50%10

  • anecdotalVarious clinical studies have showcased Syn-Ake's ability to provide significant anti-wrinkle benefits10

  • anecdotalEarly research showed this peptide could modulate muscle contraction through skin delivery12

  • anecdotalThe famous '52% wrinkle reduction at 4% in 28 days' number traces to a Pentapharm supplier brochure reproduced in trade press, not a peer-reviewed study14

  • anecdotalManufacturer-sponsored clinical data reports wrinkle depth reductions of up to 52% after 28 days of twice-daily application at 4% concentration15

  • theoreticalSyn-AKE may potentially diminish wrinkles by freezing muscles responsible for creating root creases6

How it works

Based on 5 animal findings, 18 in vitro findings, 19 expert opinion findings, 4 anecdotal findings and 15 theoretical findings.

  • animalSyn-AKE may act to reduce transmission between muscles and nerves, working similarly to botulinum toxin to relax muscles and thus reduce instances of creasing and wrinkle development2

  • animalThe synthetic equivalent of the Waglerin-1 peptide appears to temporarily reduce contractile force in certain muscle groups2

  • animalSyn-AKE appears to be a competitive antagonist of acetylcholine receptors in the muscles2

  • animalSyn-AKE may compete with acetylcholine to attach to the acetylcholine receptors and block them, thereby inhibiting the muscular impulse2

  • animalSyn-AKE targets specifically the N-acetylcholine receptors that mediate the impulse between nerve tissue and muscle tissues2

  • in vitroSyn-Ake peptide interacts with matrix metalloproteinases (MMPs) and Sirtuin 1 (SIRT1), which are targets of anti-aging activities1

  • in vitroMolecular docking study showed docking score energy of MMP receptors in the order of MMP-13 < MMP-8 < MMP-11

  • in vitroSyn-Ake peptide provided the lowest and most stable binding to SIRT1 receptor at -9.32 kcal/mol1

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  • in vitroSyn-Ake peptide remained stable in the active site of MMP-13 and SIRT1 receptors during 50 ns molecular dynamic simulations1

  • in vitroSyn-Ake demonstrated concentration-dependent increased DPPH radical scavenging activity1

  • in vitroIn vitro binding studies confirmed SYN-AKE's selectivity for the muscular-type nAChR over neuronal subtypes.3

  • in vitroIn vitro the peptide cosmetic ingredient is considered as an antagonist at the muscular nicotinic acetylcholine receptor (mnAChR)4

  • in vitroAs the muscular nicotinic ACh receptors are reversibly blocked, the ion channel remains closed. There is no uptake of Na+ and the muscle cells stay relaxed4

  • in vitroThe transmission of nerve impulses to the muscles is inhibited and facial muscles are relaxed4

  • in vitroSYN-AKE acts as a competitive antagonist at the muscular nicotinic acetylcholine receptor (mnAChR)5

  • in vitroSYN-AKE competes for the acetylcholine receptor binding site, reducing the efficiency of signal transduction without blocking it completely5

  • in vitroSnake venom tripeptide acts on the postsynaptic membrane and is a reversible antagonist of muscle nicotinic acetylcholine receptors (nmAChR)8

  • in vitroIn silico and in vitro analysis showed Syn-Ake peptide bound stably to MMP-13 and SIRT1 receptors11

  • in vitroIn vitro analysis demonstrated Syn-Ake peptide has antioxidant activity with concentration-dependent DPPH radical scavenging11

  • in vitroWaglerin-1 produces neuromuscular paralysis through selective post-synaptic blockade of the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction15

  • in vitroWaglerin-1 is selective for the epsilon-subunit-containing adult muscle nAChR, while sparing the gamma-subunit-containing fetal form15

  • in vitroWaglerin-1 is a 22-amino-acid disulfide-containing peptide with molecular weight approximately 2.6 kDa from the venom of Tropidolaemus wagleri15

  • in vitroWaglerin-1 binds to the nicotinic acetylcholine receptor at the post-synaptic muscle membrane and blocks the acetylcholine binding site on the receptor15

  • expert opinionApitegromab represents a clear advancement over ACE-031 in myostatin pathway therapeutics with selective targeting of proMyostatin and latent myostatin7

  • expert opinionMelanotan-1 is the unregulated research peptide version available from non-pharmaceutical sources with identical pharmacology to afamelanotide7

  • expert opinionSyn-Ake peptide is a synthetic tripeptide mimicking temple viper venom to reduce wrinkles and expression lines9

  • expert opinionSyn-Ake works by mimicking Waglerin-1 (temple viper venom component) to block acetylcholine receptors causing muscle contractions9

  • expert opinionSyn-Ake consists of glycerin, water, and the active dipeptide diaminobutyroyl benzylamide diacetate9

  • expert opinionSyn-Ake acts as antagonist at muscular nicotinic acetylcholine receptors (mnAChR)9

  • expert opinionSyn-Ake binds reversibly to receptors with effects that diminish when application stops9

  • expert opinionSyn-Ake works locally on facial muscles without systemic distribution9

  • expert opinionSYN-AKE has well-characterized pharmacology with defined receptor actions11

  • expert opinionSyn-AKE enables investigation of acetylcholine receptor antagonism through dermal delivery12

  • expert opinionSyn-AKE may influence neuromuscular activity and skin aging through several mechanisms12

  • expert opinionSyn-AKE's multi-target approach combines neuromuscular receptor antagonism with antioxidant activity and potential MMP modulation12

  • expert opinionSyn-Ake is a synthetic peptide inspired by waglerin-1, a neurotoxin from the temple viper13

  • expert opinionTopical creams reaching the muscle junctions several millimeters below the skin surface is something no peptide has ever been proven to do13

  • expert opinionSyn-Ake is a dipeptide derivative — structurally nothing like the 22-amino-acid waglerin-1 peptide it claims to mimic13

  • expert opinionSyn-Ake is a dipeptide modeled on snake venom, specifically designed to mimic waglerin-1, a 22-amino-acid neurotoxin from Wagler's pit viper14

  • expert opinionWaglerin-1 selectively antagonizes the muscle-type (α1-containing) nicotinic acetylcholine receptor14

  • expert opinionSYN-AKE was designed to mimic the activity of Waglerin-1, a 22-amino-acid peptide toxin from the venom of the Temple Viper (Tropidolaemus wagleri)15

  • expert opinionSYN-AKE is designed to function as a competitive antagonist at the same nAChR target as waglerin-115

  • anecdotalSyn-Ake acts to reduce muscle cell contractions, leading to a smoother skin surface, especially in areas with expression lines10

  • anecdotalSyn-Ake is a peptide that mimics the effects of snake venom, helping to relax facial muscles10

  • anecdotalPeptides signal the skin to produce more collagen, which can lead to a smoother and more youthful complexion10

  • anecdotalSyn-Ake's use can indirectly support collagen production over time by preventing repetitive muscle movements that can lead to wrinkles10

  • theoreticalSyn-AKE appears to mimic the actions of the Waglerin-1 peptide, which is 21 amino acids in length2

  • theoreticalSYN-AKE is a synthetic tripeptide that mimics waglerin-1 from the Temple Viper (Tropidolaemus wagleri), acting as a competitive antagonist at the muscular nicotinic acetylcholine receptor to reduce facial muscle contractions and expression lines.3

  • theoreticalSYN-AKE acts postsynaptically at the muscle cell's acetylcholine receptor itself, making it the only cosmetic peptide that directly targets the receptor rather than the neurotransmitter release machinery.3

  • theoreticalSYN-AKE acts as a reversible competitive antagonist at the muscular-type nicotinic acetylcholine receptor (alpha-1 subunit containing).3

  • theoreticalSYN-AKE enables the face to relax, reducing wrinkles but without losing the ability to help people express themselves4

  • theoreticalSYN-AKE is a synthetic tripeptide with mol weight below 500 Da4

  • theoreticalSYN-AKE mimics Waglerin-1 functionality, a peptide found in the venom of the temple viper4

  • theoreticalSYN-AKE is a patented synthetic tripeptide that mimics the paralytic action of Waglerin-1, a peptide component of the venom of the Temple Pit Viper (Tropidolaemus wagleri)5

  • theoreticalUnlike Argireline-class peptides that target the SNARE complex, SYN-AKE acts directly at the nicotinic acetylcholine receptor5

  • theoreticalSyn-AKE is designed to imitate the paralytic action of Temple Viper venom, reducing muscular contractions and creasing and wrinkling across the skin surface6

  • theoreticalSyn-AKE is a synthetic peptide patterned after Waglerin-1 peptide from Temple Viper venom6

  • theoreticalSYN-AKE peptide mimics the activity of snake venom waglerin I8

  • theoreticalIt blocks a muscle receptor that tells muscle to contract, thereby relaxing expression lines14

  • theoreticalSYN-AKE antagonizes nAChR at the post-synaptic membrane, reducing the muscle's response to acetylcholine, attenuating the repetitive contractions that cause and deepen expression wrinkles over time15

  • theoreticalSYN-AKE enables the face to relax and visibly reduces the appearance of wrinkles and expression lines16

Dosing

Based on 1 human trial finding, 1 human study finding, 11 expert opinion findings and 1 anecdotal finding.

  • human trialA double-blind, placebo-controlled clinical study evaluated SYN-AKE at 4% of commercial solution applied twice daily for 28 days.3

  • human studyA cream was applied twice daily for 4 weeks with total of 100 volunteers, 25 volunteers per group, measuring SYN-AKE (4%) effect compared to placebo4

  • expert opinionTypical use concentration is 4% in finished serum applied twice daily to forehead, crow's feet, and perioral area5

  • expert opinionLow amounts of Syn-AKE, often ranging from 1 to 4 percent, are typically found in products6

  • expert opinionThe minimum addition amount of Syn Ake peptides in products is 0.01%8

  • expert opinionEffective concentrations range 1-5% in topical formulations with 4% showing optimal results9

  • expert opinionCommercial formulations typically contain 4% active Syn-Ake in delivery systems optimized for skin penetration9

  • expert opinionLower concentrations (1-2%) provide preventive benefits, while higher concentrations (4-5%) target existing wrinkles more aggressively9

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  • expert opinionSYN-AKE should be used as directed by healthcare provider11

  • expert opinionOnce reconstituted, SYN-AKE should be kept refrigerated at 36-46°F (2-8°C)11

  • expert opinionReconstituted SYN-AKE should be used within timeframe specified on product labeling, typically 14-28 days11

  • expert opinionTypical concentration in formulations 1–4%13

  • expert opinionSyn-Ake is used cosmetically worldwide at 1–4% in leave-on serums and eye creams14

  • anecdotalIt takes 30 days to see the full effects10

How the body handles it

Based on 5 expert opinion findings and 1 theoretical finding.

  • expert opinionAfamelanotide is delivered as a controlled-release subcutaneous implant7

  • expert opinionSystemic absorption of SYN-AKE is negligible due to peptide topical application mechanism11

  • expert opinionSyn-AKE has low molecular weight (less than 500 Da) enabling effective topical penetration through the stratum corneum12

  • expert opinionNo penetration data shows it reaching facial muscles13

  • expert opinionSyn-Ake is supplied as a water-soluble white powder typically diluted to 0.05–0.1% active in a glycerin/water carrier14

  • theoreticalSYN-AKE is fast acting and long lasting, with a fully reversible effect16

Safety and side effects

Based on 2 human trial findings, 1 human study finding, 4 in vitro findings, 8 expert opinion findings and 3 anecdotal findings.

  • human trialClinical studies report no irritation, sensitization, or systemic neuromuscular effects at recommended concentrations.3

  • human trialNo tachyphylaxis or tolerance development has been observed with extended use, and the effect is fully reversible.3

  • human studyEffect is fully reversible and non-paralytic5

  • in vitroSyn-Ake peptide showed high efficacy and safety profile in in silico and in vitro analyses1

  • in vitroSafe dose of Syn-Ake peptide was determined through safety investigation1

  • in vitroCytotoxicity was assessed using MTT test1

  • in vitroGenotoxicity was assessed using Ames test1

  • expert opinionSYN-AKE is approved as an OTC cosmetic ingredient in EU and US5

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  • expert opinionSYN-AKE demonstrates excellent topical tolerability with no serious adverse events reported in cosmetic use spanning 15+ years11

  • expert opinionOccasional mild tingling or slight dryness are expected local skin responses with SYN-AKE rather than true adverse effects11

  • expert opinionComprehensive clinical trials examining long-term safety, optimal dosing, and mechanism validation remain limited12

  • expert opinionThe native snake-venom peptide (waglerin-1) has well-characterized toxicology14

  • expert opinionSyn-Ake is listed in the European Cosmetic Ingredients Database (CosIng) without restriction14

  • expert opinionSyn-Ake is permitted as a leave-on cosmetic ingredient in essentially every regulated cosmetic market globally14

  • expert opinionIndependent academic validation remains limited, and fundamental questions about whether topically applied peptides can penetrate to the neuromuscular junction in sufficient concentrations persist15

  • anecdotalMild tingling at application site is a reported side effect5

  • anecdotalRare redness is a reported side effect5

  • anecdotalThe first public dataset of anecdotal peptide side-effect reports, aggregated from Reddit, research forums, and anonymous user submissions7

What people use it for

Based on 15 expert opinion findings, 1 anecdotal finding and 3 theoretical findings.

  • expert opinionSyn-AKE may be practical for skin cell studies in various formulations6

  • expert opinionSynthetic peptides have been developed to reduce the appearance of wrinkles and pigmentation and enhance the skin's natural capacity to defend itself6

  • expert opinionVisible improvements appear within 5-7 days with peak effects at 28 days9

  • expert opinionWorks synergistically with copper peptides (GHK-Cu), hyaluronic acid, and other anti-aging peptides9

  • expert opinionProvides non-invasive alternative to Botox with fully reversible effects9

  • expert opinionSYN-AKE is applied topically to clean, dry skin and is not affected by food intake11

  • expert opinionSYN-AKE is indicated for rapid-acting topical wrinkle reduction for expression lines11

  • expert opinionSYN-AKE can extend or complement botulinum toxin injection results11

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  • expert opinionSYN-AKE is used for crow's feet, forehead lines, and glabellar wrinkles from muscle movement11

  • expert opinionSyn-AKE is a synthetic peptide studied for topical neuromuscular modulation in wrinkle formation and expression line research models12

  • expert opinionSyn-AKE offers researchers a topical-application model for studying neuromuscular modulation and expression line formation12

  • expert opinionSyn-AKE has not been studied via injection routes12

  • expert opinionMarketing pitch: it blocks the same nerve-to-muscle signals that Botox blocks, smoothing expression lines without needles13

  • expert opinionSYN-AKE aims to achieve a mild, reversible reduction in muscle contraction when applied topically to the skin overlying facial expression muscles15

  • expert opinionSYN-AKE is not regulated as drug and is marketed as cosmetic ingredient15

  • anecdotalMany users report noticeable reductions in the appearance of fine lines and wrinkles in a relatively short amount of time when using products containing Syn-Ake10

  • theoreticalSYN-AKE is a small synthetic peptide that helps reduce the appearance of wrinkles and laughter lines4

  • theoreticalSYN-AKE works by transiently relaxing facial muscles responsible for expression wrinkles5

  • theoreticalSYN-AKE is a small, patented, synthetic peptide that helps reduce the appearance of wrinkles and laughter lines16

Other findings

Based on 10 expert opinion findings and 6 theoretical findings.

  • expert opinionSYN-AKE was developed by DSM (formerly Pentapharm)5

  • expert opinionAll published evidence is from the manufacturer or cosmetic ingredient suppliers; no independent RCTs as of 20265

  • expert opinionPeptide Protocol Wiki is a comprehensive peptide research database featuring 133+ evidence-based peptide profiles with dosing protocols, mechanism of action breakdowns, and clinical research summaries7

  • expert opinionWrinkle-smoothing peptide (Syn-Ake) should be stored in a sealed container, away from light and humidity, in a clean place at a temperature of 15-25°C8

  • expert opinionSYN-AKE can be treated in heat (70°C for less than 2 hours) or cold8

  • expert opinionSyn-Ake (INCI: Dipeptide Diaminobutyroyl Benzylamide Diacetate) is patented synthetic tripeptide developed by Swiss company Pentapharm Ltd9

  • expert opinionSyn-Ake tolerates room temperature storage in sealed containers9

  • expert opinionSyn-AKE is a synthetic tripeptide first developed in Switzerland in 200612

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  • expert opinionThe molecule is supplied as the diacetate salt14

  • expert opinionSYN-AKE is a synthetic tripeptide developed by Pentapharm (now part of DSM) as a cosmeceutical anti-wrinkle ingredient inspired by the neurotoxic mechanism of snake venom15

  • theoreticalSyn-AKE is also known as tripeptide-3 or dipeptide diaminobutyroyl benzyl amide diacetate2

  • theoreticalMolecular weight approximately 390 Da13

  • theoreticalSYN-AKE is miscible with water16

  • theoreticalSYN-AKE is insoluble in lipophilic components16

  • theoreticalSYN-AKE can be processed up to 2 hours at 70°C16

  • theoreticalSYN-AKE shows very good compatibility with emulsifier systems, emollients, waxes, preservatives, hydrocolloids, sunscreens, detergents and other commonly used substances16

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Limited evidence

No independent peer-reviewed human RCTs exist; skin penetration to muscle is unproven

Multiple sources note independent academic validation is limited, all published human evidence traces to the manufacturer or ingredient suppliers, no independent RCTs exist as of 2026, no published lab study confirms receptor blockade, and no penetration data show the peptide reaching neuromuscular junctions millimeters below the skin (SYN-AKE (Dipeptide Diaminobutyroyl Benzylamide Diacetate): Research Evidence & Safety Profile | PeptideInsight, Syn-Ake: Research, Evidence & Safety | Peptidings, SYN-AKE: Snake Venom Peptide Research & Skin Benefits, Syn-Ake: The Snake-Venom-Inspired Wrinkle Peptide | Kalios, Syn-AKE Peptide | USA Made | Topical Research Grade).

Single source

MMP/SIRT1 and antioxidant mechanisms come from a single in silico/in vitro study

The claims that Syn-Ake interacts with MMPs and SIRT1 (SIRT1 binding -9.32 kcal/mol) and has DPPH antioxidant activity derive from one PubMed-indexed in silico/in vitro study (Anti-aging activity of Syn-Ake peptide by in silico approaches and in vitro tests), echoed by SYN-AKE Dosing, Need to Know Information, Safety,… | Peptide Initiative; these are computational/lab findings, not clinical.

Inconsistency

The double-blind clinical trial sometimes credited to 'Lintner (2009)' as proof that Syn-Ake smooths wrinkles cannot be verified, and other reviewers say no peer-reviewed human…

One vendor guide (pepguide.io) credits a double-blind, placebo-controlled Syn-Ake study to 'Lintner et al. (2009),' reporting significant crow's-feet wrinkle reduction. Other reference sources, however, state flatly that there is not a single peer-reviewed clinical trial of Syn-Ake in humans — the only manufacturer study (roughly 45 subjects over 28 days) was never published in a medical journal, never independently replicated, and its methods were never disclosed. The frequently repeated '52% wrinkle reduction in 28 days' figure is traced to a Pentapharm supplier brochure reproduced in trade press rather than a published paper. A named, dated citation like this should therefore not be taken as evidence of a verifiable, independent trial.

Using it with other compounds

Check a stack
  • SNAP-8Complementary

    May be complementary

    Both soften dynamic wrinkles by quieting the neuromuscular junction, but from opposite sides of the synapse: SNAP-8 inhibits the presynaptic SNARE machinery that releases acetylcholine, whereas SYN-AKE blocks the postsynaptic nicotinic receptor that would receive it. Because they interrupt the same muscle-contraction signal at two different steps, combining them can give a more complete relaxation effect than either alone.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    The mechanism descriptions clearly establish that both peptides operate within the acetylcholine_pathway but at distinct anatomical locations: SNAP-8 targets presynaptic SNARE-mediated acetylcholine release (SNAP-25, SNARE complex, exocytosis), while SYN-AKE targets postsynaptic nicotinic acetylcholine receptors (mnAChR, alpha-1 subunit). Both produce muscle relaxation and wrinkle reduction through this shared pathway. The proposed relationship as 'complementary' with the shared dimension of 'acetylcholine_pathway' is directly supported by the mechanisms—they interrupt neuromuscular transmission at sequential steps (presynaptic release vs. postsynaptic reception), which justifies the claim that they could provide additive effects on muscle relaxation.

    Timing Topical use; can be layered in the same routine.

    Shares acetylcholine pathway

  • ArgirelineComplementary

    May be complementary

    Both aim to relax hyperkinetic expression muscles to soften wrinkles, but by different molecular steps: Argireline blocks the SNARE machinery that releases acetylcholine, while SYN-AKE blocks the postsynaptic nicotinic acetylcholine receptor that receives the signal. Hitting the same neuromuscular pathway at two different points can be complementary for topical line-smoothing.

    Tier 4Theoretical — not established

    What the research doesn't fully establish

    Both peptides' mechanisms clearly target the acetylcholine pathway at different molecular steps: Argireline inhibits presynaptic acetylcholine release via SNARE complex interference, while SYN-AKE blocks postsynaptic nicotinic acetylcholine receptor signaling. Both are documented to reduce wrinkle appearance through muscle relaxation. The proposed relationship as 'complementary' is justified—they act on the same neuromuscular pathway (acetylcholine_pathway, a shared approved tag) but at distinct sequential points (presynaptic vs. postsynaptic), which is a valid definition of complementary mechanism. The explanation accurately reflects the mechanism descriptions provided.

    Shares acetylcholine pathway

  • LeuphasylComplementary

    May be complementary

    SYN-AKE relaxes mimic muscles by blocking the postsynaptic nicotinic acetylcholine receptor, whereas Leuphasyl works on the presynaptic side to cut acetylcholine release. Attacking both sides of the neuromuscular junction converges on the same visible outcome — reduced expression lines — making them complementary in a smoothing topical.

    Tier 3Largely anecdotal — commonly discussed

    What the research doesn't fully establish

    The mechanisms clearly establish complementary action at the neuromuscular junction. Leuphasyl targets presynaptic enkephalin/delta-opioid receptors leading to inhibition of acetylcholine release via Gi/Go signaling and calcium channel inhibition. SYN-AKE targets postsynaptic muscular nicotinic acetylcholine receptors to block signal transmission. Both peptides are documented to reduce expression lines through neuromuscular relaxation, but via opposing sides of the synapse. The shared dimension 'acetylcholine_pathway' is explicitly supported: Leuphasyl has the approved tag 'acetylcholine_pathway' and mechanisms describing SNARE-mediated acetylcholine exocytosis inhibition; SYN-AKE has the approved tag 'acetylcholine_pathway' and mechanisms describing postsynaptic nicotinic acetylcholine receptor signaling. The explanation accurately reflects the dual-site mechanism described in both peptides' documentation, making this a well-justified complementary relationship.

    Timing Topical; can be layered together.

    Shares acetylcholine pathway

Safety and side effects

Safety & Tolerability

This is a topical cosmetic ingredient, not an injectable drug. cenexalabs.com states Syn-AKE has not been studied via injection routes (src-10).

  • 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 (src-6). 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 (src-7).
  • 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 (src-9).
  • 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 test (src-5).

Regulatory Status

peptahub.com states SYN-AKE is approved as an OTC cosmetic ingredient in the EU and US (src-6). 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 (src-8). peptideinsight.com notes it is not regulated as a drug but marketed as a cosmetic ingredient (src-2, src-6, src-11).

Important Caveats

Safety statements above derive largely from manufacturer/supplier and vendor sources. Multiple sources note there are no independent RCTs as of 2026 (src-6), that comprehensive long-term safety trials remain limited (src-10), and that the underlying mechanism and skin penetration to the neuromuscular junction remain unproven (src-3, src-13). 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 (src-8).

Reconstitution and handling

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 (src-2, src-6, src-11), and it has not been studied via injection routes (src-10). The figures below are what sources report for cosmetic formulation — not medical guidance.

Supplied raw material (DSM formulation guidelines, src-4)

  • 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 (src-11), with the diacetate salt reported at 503 Da and the free base at 432 Da by kalios.health (CAS 823202-99-9) (src-8). 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 (src-8).

Reported use concentrations

  • kalios.health: used cosmetically worldwide at 1–4% in leave-on serums and eye creams (src-8); pulse.co.ke: typically 1–4% in products (src-12); peptidings.com: typical formulation concentrations of 1–4% (src-3).
  • peptahub.com: typical use is 4% in a finished serum applied twice daily to forehead, crow's feet, and perioral areas (src-6).
  • seekpeptides.com: effective concentrations of 1–5%, with 4% described as optimal (lower 1–2% for prevention, higher 4–5% for existing wrinkles) (src-11).
  • omizzur.com: a minimum addition amount of 0.01% in products (src-13).
  • peptideinitiative.com: applied topically to clean, dry skin, not affected by food intake (src-9, src-32).

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 detergents (src-4, src-13). 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-treated (src-13, src-4). seekpeptides.com states it tolerates room-temperature storage in sealed containers (src-11), 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 (src-9).

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 (src-11); naturalorganicskincare.com states full effects take about 30 days (src-16). 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 (src-8), and peptidings.com states the sole manufacturer study was never published, replicated, or its methods disclosed (src-3).

Sources

Ordered by evidence quality — the strongest first.

  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. Buy Syn-AKE Peptide (200mg) - BiotechPeptides(opens in a new tab)
    Tier 2Web · biotechpeptides.com
  3. SYN-AKE (Dipeptide Diaminobutyroyl Benzylamide Diacetate): Research Profile, Mechanism & Protocols | PepGuide | PepGuide(opens in a new tab)
    Tier 2Web · pepguide.io
  4. SYN-AKE®(opens in a new tab)
    Tier 2Web · dsm-firmenich.com
  5. SYN-AKE: Snake Venom Peptide Research & Skin Benefits(opens in a new tab)
    Tier 2Web · peptahub.com · 2026
  6. How does Syn-AKE Peptide work? | Pulse Kenya(opens in a new tab)
    Tier 3Web · pulse.co.ke
  7. Peptide Protocol Wiki — Evidence-Based Peptide Research Database(opens in a new tab)
    Tier 3Web · peptideprotocolwiki.com
  8. Syn Ake | Omizzur Peptide(opens in a new tab)
    Tier 3Web · omizzur.com
  9. Syn Ake Peptide: Complete Guide to Benefits, Dosage & Results - SeekPeptides(opens in a new tab)
    Tier 3Web · seekpeptides.com
  10. Syn Ake Wrinkle Smoothing Peptide(opens in a new tab)
    Tier 3Web · naturalorganicskincare.com
  11. SYN-AKE Dosing, Need to Know Information, Safety,… | Peptide Initiative(opens in a new tab)
    Tier 3Web · peptideinitiative.com
  12. Syn-AKE Peptide | USA Made | Topical Research Grade(opens in a new tab)
    Tier 3Web · cenexalabs.com
  13. Syn-Ake: Research, Evidence & Safety | Peptidings(opens in a new tab)
    Tier 3Web · peptidings.com · 2026
  14. Syn-Ake: The Snake-Venom-Inspired Wrinkle Peptide | Kalios(opens in a new tab)
    Tier 3Web · kalios.health · 2026
  15. SYN-AKE (Dipeptide Diaminobutyroyl Benzylamide Diacetate): Research Evidence & Safety Profile | PeptideInsight(opens in a new tab)
    Tier 3Web · peptideinsight.com · 2026
  16. SYN®-AKE(opens in a new tab)
    Tier 4Web · dsm.com