Mdivi 1

Mdivi 1 is a mitochondrial division inhibitor.^1,2 It inhibits the GTPase activity of yeast, but not human, dynamin-1 (Dnm1; IC₅₀ = ~1-10 µM for the recombinant yeast enzyme) and human dynamin-related protein 1 (DRP1) in A549 lung cancer cells when used at a concentration of 50 µM. Mdivi 1 (50 µM) inhibits mitochondrial fragmentation and DRP1 self-assembly induced by staurosporine (Item No. 81590) in COS cells overexpressing DRP1.¹ It induces apoptosis in, and inhibits colony formation of, A549 cells when used at concentrations of 25 and 50 µM, respectively.² Mdivi 1 (1 µM) decreases doxorubicin-induced increases in infarct-to-risk ratios in a Langendorff isolated perfused rat heart model of ischemia-reperfusion injury.³ It reduces the severity of lung injury in a mouse model of LPS-induced acute lung injury when administered at a dose of 20 mg/kg.⁴

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1. Cassidy-Stone, A., Chipuk, J.E., Ingerman, E., et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev. Cell 14(2), 193-204 (2008).

2. Wu, D., Dasgupta, A., Chen, K.-H., et al. Identification of novel dynamin-related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia-reperfusion injury. The FASEB Journal 34(1), 1447-1464 (2020).

3. Gharanei, M., Hussain, A., Janneh, O., et al. Attenuation of doxorubicin-induced cardiotoxicity by mdivi-1: A mitochondrial division/mitophagy inhibitor. PLoS One 8(10), e77713 (2013).

4. Deng, S., Zhang, L., Mo, Y., et al. Mdivi-1 attenuates lipopolysaccharide-induced acute lung injury by inhibiting MAPKs, oxidative stress and apoptosis. Pulm. Pharmacol. Ther. 62, 101918 (2020).