Description
Dynasore (304448-55-3) is a noncompetitive inhibitor of dynamin GTPase activity and blocks dynamin-dependent endocytosis in cells, including neurons. It inhibits the GTPase activity of dynamin1, dynamin2, and Drp1 (mitochondrial dynamin). It is cell permeable, fast acting (seconds) and reversible.1,2 Dynasore is a extremely useful tool for studying endocytosis and other cellular events which are dependent on dynamin.3-5
Uses
Dynamin Inhibitor I, Dynasore is an inhibitor of Dynamin I and Dynamin II.
Uses
Dynasore is a cell-permeable, reversible inhibitor of dynamin 1, dynamin 2, and mitochondrial dynamin, Drp1 GTPase activity (IC50 = 15 μM). Through this action, dynasore inhibits clathrin-dependent vesicle formation and endocytosis, which is necessary for internalization of certain parasites and viruses, as well as particles and receptor ligands. In some cases, dynasore can also augment the release of neurotransmitters and secreted cytokines.[Cayman Chemical]
Definition
ChEBI: A carbohydrazide resulting from the formal condensation of the hydrazone moiety of 3,4-dihydroxybenzaldehyde hydrazone with the carboxy group of 3-hydroxy-2-naphthoic acid. It is a cell-permeable, reversible noncompetitive inhibitor of the GTPase activity
f dynamin 1 and 2 and Drp1 (mitochondrial), while exhibiting no significant effect against two other small GTPases, MxA and Cdc42.
Biological Activity
Non-competitive inhibitor of dynamin 1, dynamin 2 and mitochondrial dynamin (Drp1) GTPase activity. Does not inhibit other small GTPases. Blocks endocytic pathways dependent on dynamin and inhibits cell spreading and migration of BSC1 cells.
Background
Dynasore is a cell-permeable, small-molecule inhibitor of the endocytosis-associated GTPase dynamin. Dynamin promotes clathrin-coated vesicle formation and is involved in detaching coated pits from the membrane during clathrin-mediated endocytosis. Dynasore inhibits the GTPase activity of dynamin I, dynamin II, dynamin-related protein 1, and mitochondrial dynamin. By blocking dynamin, Dynasore inhibits coated vesicle formation and dynamin-mediated endocytic pathways. In a study of hippocampal synapses, inhibition by Dynasore demonstrated that dynamin is essential for all forms of synaptic vesicle endocytosis, and that Dynasore has no effect on exocytosis. A study of hepatocellular carcinoma demonstrated that Dynasore enhanced the inhibitory effects of c-Met inhibitors on hepatoma cell proliferation and migration, and led to increased cell cycle arrest and apoptosis. Dynasore blocked HSV-1 entry into human and murine keratinocytes, and prevented HSV-1 and HSV-2 infection of human epithelial and neuronal cells, including primary genital tract cells and human fetal neurons and astrocytes.
References
[1] ERIC MACIA. Dynasore, a cell-permeable inhibitor of dynamin.[J]. Developmental cell, 2006, 10 6: 839-850. DOI:
10.1016/j.devcel.2006.04.002[2] TOM KIRCHHAUSEN H E P Eric Macia. Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of endocytosis.[J]. Methods in enzymology, 2008, 438: 77-93. DOI:
10.1016/s0076-6879(07)38006-3[3] WENBO LU. Dynamin and activity regulate synaptic vesicle recycling in sympathetic neurons.[J]. The Journal of Biological Chemistry, 2009, 284 3: 1930-1937. DOI:
10.1074/jbc.m803691200[4] CHIHYE CHUNG. Acute dynamin inhibition dissects synaptic vesicle recycling pathways that drive spontaneous and evoked neurotransmission.[J]. Journal of Neuroscience, 2010, 30 4: 1363-1376. DOI:
10.1523/jneurosci.3427-09.2010[5] STEVE POIRIER. Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route.[J]. The Journal of Biological Chemistry, 2009: 28856-28864. DOI:
10.1074/jbc.m109.037085
