Mdivi-1

Names

[ Name ]:
Mdivi-1

[Synonym ]:
4(1H)-Quinazolinone, 3-(2,4-dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-
HMS575G09
3-(2,4-Dichloro-5-methoxyphenyl)-2-thioxo-2,3-dihydro-4(1H)-quinazolinone
Mdivi-1
3-(2,4-Dichloro-5-methoxyphenyl)-2-sulfanylquinazolin-4(3H)-one
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone
Mitochondrial division inhibitor 1

Biological Activity

[Description]:

Mdivi-1 is a selective dynamin-related protein 1 (Drp1) inhibitor.

[Related Catalog]:

Signaling Pathways >> Cytoskeleton >> Dynamin

Research 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.

[Related Small Molecules]

Dynasore

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

[ Storage condition ]:
Store at -20°C

[ Water Solubility ]:
DMSO: >20mg/mL

Safety Information

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Dynamin-related protein Drp1 and mitochondria are important for Shigella flexneri infection.

Int. J. Med. Microbiol. 304(5-6) , 530-41, (2014)

Shigella infection in epithelial cells induces cell death which is accompanied by mitochondrial dysfunction. In this study the role of the mitochondrial fission protein, Drp1 during Shigella infection...

Related Compounds

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