Dyngo-4a
Dyngo-4a(CAS 1256493-34-1) is a dynamin inhibitor that modulates cellular endocytic processes by targeting dynamin isoforms, including DynI and DynII. It inhibits DynI (brain-derived), DynI (recombinant), and DynII (recombinant) activity with IC50 values of approximately 0.38 μM, 1.1 μM, and 2.3 μM respectively. Mechanistically, Dyngo-4a blocks dynamin-mediated vesicle scission, thereby interfering with clathrin-dependent endocytosis. In cell culture, Dyngo-4a reduces β-catenin levels in human cancer cell lines and prevents uptake of botulinum toxin type A (BoNT/A) into hippocampal neurons, blocking toxin-induced cleavage of SNAP25 protein. In rodent models, systemic administration of Dyngo-4a delays muscle paralysis induced by botulinum neurotoxin, highlighting its potential as a research tool in studies of dynamin-dependent signaling pathways and membrane trafficking events.
References:
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.
- 1. Shane C Wright, Aikaterini Motso, et al. "GLP-1R signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics." Nat Commun. 2023 Oct 9;14(1):6243. PMID: 37813859
- 2. Morales Rodriguez, Loyda. "Location-Biased Signaling of Proton-Sensing Receptor GPR65 Within the Endocytic Pathway." University of Michigan Library 2023
| Storage | Store at -20°C |
| M.Wt | 338.31 |
| Cas No. | 1256493-34-1 |
| Formula | C18H14N2O5 |
| Solubility | ≥33.8 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | (E)-3-hydroxy-N'-(2,4,5-trihydroxybenzylidene)-2-naphthohydrazide |
| SDF | Download SDF |
| Canonical SMILES | Oc(cc1O)c(/C=N/NC(c2cc(cccc3)c3cc2O)=O)cc1O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Kinase assays |
For analysis of the kinetics of inhibition, dynamin I at a final concentration of 17 nM was incubated with GTPase buffer containing PS (2 μg/mL) and varying amounts of GTP (50–250 μM) in the presence of 4a at a concentration range between 0.5 and 6 μM. The reaction was stopped after 30 min by addition of EDTA (0.5 mM, pH7.4). |
| Cell experiment [1]: | |
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Cell lines |
U2OS cell lines |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1~100 μM |
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Applications |
Dyngo-4a potently inhibited Tfn endocytosis with IC50 values of 5.7±1.0 μM, approximating the activity of the most potent small molecule endocytosis inhibitors previously reported. |
| Animal experiment [2]: | |
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Animal models |
Female CD-1 mice |
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Dosage form |
30 mg/kg, intraperitoneal injection |
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Application |
Mice injected with Dyngo-4a took significantly longer to exhibit clear signs of botulism which indicates that Dyngo-4a pretreatment provides significant protection against botulism. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [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] 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. |
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Quality Control & MSDS
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Chemical structure
