Background:

Target: DynI (brain); DynI (rec); DynII (rec)

IC50: 0.38 μM; 1.1 μM; 2.3 μM

Dyngo-4a is a potent, novel dynamin inhibitor with IC50 values of 0.38 μM, 1.1 μM, and 2.3 μM for DynI (brain), DynI (rec), and DynII (rec), respectively [1]. Dynamin is a large GTPase enzyme that severs as membrane-bound clathrin-coated vesicles [1].

In vitro: Dyngo-4a (100 μM) caused a reduction in β-catenin levels in human colon carcinoma RKO cells [2]. In addition, Dyngo-4a prevented the uptake of BoNT/A-Hc and blocked BoNT/A-induced SNAP25 cleavage in cultured hippocampal neurons [3]. Dyngo-4a is potent, reversible endocytosis inhibitor in non-neuronal cells. Dyngo-4a inhibited synaptic vesicle endocytosis (SVE) in synaptosomes and neurons with an IC50 value of 26.8 μM [1].

In vivo: Dynamin is a potential therapeutic target for counteracting botulism. Dyngo-4a (30 mg/kg, intraperitoneal injection) treatment suppressed BoNT/A-induced muscle paralysis at the rat hemidiaphragm and significantly delayed the onset of botulism in an in vivo murine model [3].

参考文献:
1.  McCluskey A, Daniel JA, Hadzic G, Chau N, Clayton EL, Mariana A, et al. Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis. Traffic. 2013;14(12):1272-89.
2.  Gagliardi M, Hernandez A, McGough IJ, Vincent JP. Inhibitors of endocytosis prevent Wnt/Wingless signalling by reducing the level of basal beta-catenin/Armadillo. J Cell Sci. 2014;127(Pt 22):4918-26.
3.  Harper CB, Martin S, Nguyen TH, Daniels SJ, Lavidis NA, Popoff MR, et al. Dynamin inhibition blocks botulinum neurotoxin type A endocytosis in neurons and delays botulism. J Biol Chem. 2011;286(41):35966-76.