product name Mdivi-1
Description: Mdivi-1 is a selective cell-permeable inhibitor of mitochondrial division DRP1 (dynamin-related GTPase) and mitochondrial division Dynamin I (Dnm1) with IC50 of 1-10 μM. Mdivi-1 inhibits apoptosis by inhibiting mitochondrial outer membrane permeabilization. Mdivi-1 is the first selective inhibitor of mitochondrial division dynamins. Mdivi-1 represents a class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases.
References: Dev Cell. 2008 Feb;14(2):193-204; Invest Ophthalmol Vis Sci. 2011 Apr 27;52(5):2837-43.
353.22
Formula
C15H10Cl2N2O2S
CAS No.
338967-87-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 70 mg/mL (198.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+40% PEG 300+ddH2O: 7mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19415318
| In Vitro |
In vitro activity: Mdivi-1 is a cell-permeable quinazolinone compound that inhibits yeast (Dnm1) and mammalian (Drp1) division DRPs (dynamin-related GTPases) and effectively induces mitochondrial fusion into net-like structures in a reversible manner. Cell-free studies indicate that mdivi-1 blocks Dnm1 ATPase activity (IC50<10 μM) and self-assembly by an allosteric modulation-based mechanism. Mdivi-1 is shown to effectively suppress STS- as well as C8-Bid-induced MOMP (Mitochondrial Outer Membrane Permeabilization) in HeLa cultures and in cell-free murine liver mitochondria preparations, respectively, as assessed by cytochrome C release. In cells, mdivi-1 retards apoptosis by inhibiting mitochondrial outer membrane permeabilization. In principle, mivi-1 represents a class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases. Kinase Assay: Cell Assay: The most efficacious inhibitor, mdivi-1 attenuates mitochondrial division in yeast and mammalian cells by selectively inhibiting the mitochondrial Drp1-mediated division dynamin. Mdivi-1 potently blocks Bid-activated Bax/Bak-dependent cytochrome c release from mitochondria. |
|---|---|
| In Vivo | Drp1 and GFAP protein expression is significantly increased in the early neurodegenerative events of ischemic mouse retina. Mdivi-1 treatment blocks apoptotic cell death in ischemic retina, and significantly increases RGC survival at 2 weeks after ischemia. In the normal mouse retina, Drp1 is expressed in the ganglion cell layer (GCL) as well as the inner plexiform layer, the inner nuclear layer (INL), and the outer plexiform layer (OPL). In the GCL, Drp1 immunoreactivity is strong in RGCs. While Drp1 protein expression is increased in the GCL of vehicle-treated ischemic retina at 12 hours. Mdivi-1 treatment does not change this increase of Drp1 protein expression but significantly decreased GFAP protein expression. |
| Animal model | C57BL/6 mice |
| Formulation & Dosage | Dissolved in DMSO; 50 mg/kg; i.p. injection |
| References | Dev Cell. 2008 Feb;14(2):193-204; Invest Ophthalmol Vis Sci. 2011 Apr 27;52(5):2837-43. |
