Syn-AKE

Also known as: Dipeptide Diaminobutyroyl Benzylamide Diacetate, SYN-AKE, DABBA, Tripeptide-3

Evidence: Clinical

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Overview

Small peptidomimetic (beta-Ala-Pro-Dab benzylamide, sold as the diacetate) modeled on viper waglerin-1; one manufacturer-run RCT (n=57) found less forehead frown-line area at 4 weeks.

Syn-AKE (INCI dipeptide diaminobutyroyl benzylamide diacetate) is a small synthetic molecule from Pentapharm, now DSM, built from beta-alanine, proline and diaminobutyric acid benzylamide. It is described as a mimic of waglerin-1, a 22-residue peptide from Tropidolaemus wagleri venom (Debono et al., 2017). The one published randomized, double-blind, placebo-controlled trial was run by DSM: 57 adults aged 50 to 65 applied 4% of a trade product holding 2500 ppm of the compound twice daily, and after 4 weeks the active group had less forehead wrinkle area and length when frowning (Campiche et al., 2021). The '52% in 28 days' figure is manufacturer data with no published trial behind it (Errante et al., 2020). Other human data come from a L'Oreal serum that also contains acetyl hexapeptide-8 (Zhu et al., 2026).

Benefits

Forehead frown-line area and length reduction at 4 weeks (human RCT, manufacturer-run, n=57), antioxidant activity and predicted MMP and SIRT1 binding (in vitro, in silico); muscle relaxation itself is unmeasured

Dosing reference

Research dose: Topical. 4% of a trade product containing 2500 ppm of the compound (about 0.01% compound) in the one published RCT; a combination serum lists 2%.

Topical only. The RCT applied a nickel-sized amount (2 mg/cm2) over the whole face twice daily for 4 weeks, using 4% of a trade product that holds 2500 ppm of the compound. A combination serum used alongside botulinum toxin injections lists 2% of the ingredient (Lupin et al., 2024).

Mechanism

Proposed, by analogy to the parent toxin. Waglerin-1 is a competitive antagonist of the adult (epsilon-subunit) muscle nicotinic acetylcholine receptor; it blocked end-plate responses in adult mice with an IC50 of 50 nM (McArdle et al., 1999). Waglerin-1 binds human receptors about 100-fold less tightly than mouse receptors (Molles et al., 2002). The manufacturer states that Syn-AKE blocks the same receptor reversibly; no peer-reviewed study has measured its receptor binding, end-plate effect or skin penetration. Independent work is limited to docking against MMPs and SIRT1 and a DPPH antioxidant assay (Gok et al., 2024).

Evidence

Clinical: at least one published human trial or an approved drug

Randomized, double-blind, placebo-controlled trial in 57 adults aged 50 to 65: 4% of a trade product (2500 ppm compound) twice daily for 4 weeks reduced forehead wrinkle area and length when frowning versus placebo, p<0.05 (Campiche et al., 2021)
Concentration-dependent DPPH radical scavenging; no cytotoxicity (MTT) or mutagenicity (Ames) at the tested doses; docking predicts MMP-13 and SIRT1 binding (Gok et al., 2024)
A serum combining the compound with acetyl hexapeptide-8, gluconolactone and niacinamide improved static and dynamic wrinkles over 12 weeks in two studies (n=50, n=42) with no control arm stated in the abstract (Zhu et al., 2026)
Parent toxin waglerin-1 selectively blocks the adult mouse muscle nicotinic receptor (McArdle et al., 1999)
Human-trial status: one published RCT of the compound alone (n=57, 4 weeks), run by the manufacturer; other human data use combination serums

References

Side effects

No cytotoxicity or mutagenicity at the tested doses in vitro (Gok et al., 2024). The parent toxin waglerin-1 is lethal to adult mice through neuromuscular block (McArdle et al., 1999); the topical mimetic has no published systemic exposure or toxicity data in animals or people. Tolerability results from the RCT are not given in its abstract. Commonly reported (anecdotal): mild irritation.

Storage

Storage: Room temperature, away from light
Lyophilized: 2 years at room temp
Reconstituted: N/A (ready to use)

Pharmacology

Half-life: No published pharmacokinetic data in any species
Bioavailability: Not measured; no published skin-penetration data. Reaching the muscle receptor is unproven
Molecular weight: 375.47 Da
Sequence: [beta-Ala]-Pro-[Dab]-[NH-benzyl]