Mdivi-1

• CAT Number: I013913
• CAS Number: 338967-87-6
• Molecular Formula: C15H10Cl2N2O2S
• Molecular Weight: 353.22
• Purity: ≥95%
• Synonyms: 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanylidene-1H-quinazolin-4-one
• InChI: InChI=1S/C15H10Cl2N2O2S/c1-21-13-7-12(9(16)6-10(13)17)19-14(20)8-4-2-3-5-11(8)18-15(19)22/h2-7H,1H3,(H,18,22)
• InChIKey: NZJKEVWTYMOYOR-UHFFFAOYSA-N
• SMILES: COC1=C(C=C(C(=C1)N2C(=O)C3=CC=CC=C3NC2=S)Cl)Cl

Mdivi-1 is a selective dynamin-related protein 1 (Drp1) inhibitor. Mdivi-1 is a mitochondrial division/mitophagy inhibitor.
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].
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].

Reference

[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.
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[2]. Tanaka A, et al. A chemical inhibitor of DRP1 uncouples mitochondrial fission and apoptosis. Mol Cell. 2008 Feb 29;29(4):409-10.
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[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.
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