Introduction：Basic information about CAS 338967-87-6|Mdivi-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Mdivi-1 is a selective dynamin-related protein 1 (Drp1) inhibitor.
Related Catalog
Signaling Pathways >>Cytoskeleton >>DynaminResearch Areas >>Cancer
In Vitro
Mdivi-1 inhibits Dnm1 GTPase activity in a dose-dependent manner, with an estimated EC50 of 1-10 μM. Mdivi-1 increases the apparent K0.5 for GTP, lowers the apparent Vmax for GTP hydrolysis, and causes an increase in the Hill coefficient observed for GTP in the Dnm1 GTP hydrolysis reaction[1]. Cells treated with mdivi-1 display decreased cytochrome c release and a reduced rate of phosphatidylserine exposure on their surface following apoptosis induction, consistent with an inhibition of apoptosis and with previous studies using other strategies to compromise DRP1 activity[2]. Mdivi-1 results in apoptotic cell death in ischemic retina[3].
In Vivo
The mitochondrial division DRP, Dnm1, is the target of mdivi-1 in vivo. Mdivi-1 quantitatively blocks GMPPCP- dependent Dnm1 self-assembly in a concentration range similar to its effects on mitochondrial division in vivo[1]. Mdivi-1 (50 mg/kg, i.p.) significantly decreases GFAP protein expression in the normal mouse retina[3].
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
YPGlycerol plates are topped with 10 mL YPGlycerol containing 1% low melt agar and 75 μM mdivi-1, and cells are spotted 12 hours later using a 48 well pinning device. After pinning cells, plates are incubated at 24°C or 37°C and imaged using an Eagle Eye II imaging system.
References
[1]. Cassidy-Stone A, et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008 Feb;14(2):193-204.
[2]. Tanaka A, et al. A chemical inhibitor of DRP1 uncouples mitochondrial fission and apoptosis. Mol Cell. 2008 Feb 29;29(4):409-10.
[3]. Park SW, et al. A selective inhibitor of drp1, mdivi-1, increases retinal ganglion cell survival in acute ischemic mouse retina. Invest Ophthalmol Vis Sci. 2011 Apr 27;52(5):2837-43.
[4]. Zhou K, et al. RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage. Exp Neurol. 2017 Sep;295:116-124.
Chemical & Physical Properties
Density
1.6±0.1 g/cm3
Boiling Point
522.5±60.0 °C at 760 mmHg
Melting Point
289 °C
Molecular Formula
C15H10Cl2N2O2S
Molecular Weight
353.223
Flash Point
269.8±32.9 °C
Exact Mass
351.984009
PSA
82.92000
LogP
3.85
Vapour Pressure
0.0±1.4 mmHg at 25°C
Index of Refraction
1.729
InChIKey
NZJKEVWTYMOYOR-UHFFFAOYSA-N
SMILES
COc1cc(-n2c(=S)[nH]c3ccccc3c2=O)c(Cl)cc1Cl
Storage condition
Store at -20°C
Water Solubility
DMSO: >20mg/mL
Safety Information
Hazard Codes
Xi
RIDADR
NONH for all modes of transport
Articles1
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