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    Mdivi-1 (Mitochondrial division inhibitor 1)
    Mdivi-1 (Mitochondrial division inhibitor 1)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1591
    CAS #: 338967-87-6Purity ≥98%

    Description: Mdivi-1 (Mitochondrial Division Inhibitor 1; Mdivi 1; Mdivi1) is a potent selective and cell-permeable inhibitor of mitochondrial division DRP1 (dynamin-related GTPase) and mitochondrial division Dynamin I (Dnm1) with the potential for treating stroke, myocardial infarction, and neurodegenerative disease. It inhibits DRP1 and Dnm1 with IC50s of 1-10 μM. Mdivi-1 inhibits apoptosis by inhibiting mitochondrial outer membrane permeabilization. Mdivi-1 treatment blocked apoptotic cell death in ischemic retina, and significantly increased RGC survival at 2 weeks after ischemia. Mdivi-1 is the first selective inhibitor of mitochondrial division dynamins and 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.

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    Molecular Weight (MW)353.22
    FormulaC15H10Cl2N2O2S
    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

    Mdivi-1; Mitochondrial Division Inhibitor 1; Mdivi 1; Mdivi1.

    Chemical Name: 3-(2,4-dichloro-5-methoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one

    SMILES Code: O=C1N(C2=CC(OC)=C(Cl)C=C2Cl)C(NC3=C1C=CC=C3)=S

    Exact Mass: 351.984 


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    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: All GTPase assay reactions are started in a 200 μL volume, of which 150 μL is placed into the well of a 96-well plate. Depletion of NADH, as monitored by reading the A340 of the reaction, is measured every 20 s for a total of 40 min using a SpectraMAX 250 96-well plate reader. Spectrophotometric data are transferred to Excel and the measured steady state depletion of NADH over time is converted to protein activity.


    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 VivoDrp1 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 modelC57BL/6 mice 
    Formulation & DosageDissolved in DMSO; 50 mg/kg; i.p. injection 
    ReferencesDev Cell. 2008 Feb;14(2):193-204; Invest Ophthalmol Vis Sci. 2011 Apr 27;52(5):2837-43.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Mdivi-1

    Chemical screen for mitochondrial division inhibitors. Dev Cell. 2008 Feb;14(2):193-204.
     

    Mdivi-1

    The target of mdivi-1 is the mitochondrial division dynamin, Dnm1. Dev Cell. 2008 Feb;14(2):193-204.
     

    Mdivi-1

    mdivi-1 and its active analogs attenuate apoptosis. Dev Cell. 2008 Feb;14(2):193-204.


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