Mdivi-1, derivative of quinazolinone, is a selective inhibitor of mitochondrial division by targeting Dnm1 (dynamin-1) and DRP (dynamin-related protein).
In mammalian cells (COS cell), mdivi-1 inhibits mitochondrial division with IC50 of 50 μM by specially inhibiting DRP1 activity, and in Hela cell, mdivi-1 impedes apoptosis early in the intrinsic pathway by attenuating Bak/Bax dependent MOMP (mitochondrial outer membrane permeabilization)[3].
It has been shown to reduce seizure activity and increase survival of KA-reduced mice intravenously injected of 20 mg/kg mdivi-1 by protecting mitochondrial morphology and attenuating cell death in the hippocampus[4]. In the study of ischemia reperfusion injury, mdivi-1 can protect against ischemia reperfusion injury of spinal cord neurons and mitochondrial dysfunction in vivo through activating BK channels dependently in SD rat which were treated with intravenous bolus of 1 mg/kg[5]. The function of mdivi-1 is also reflected in the protection of ischemic retina. Research has shown that mdivi-1 can reverse cell apoptosis caused by transient retinal ischemia and significantly increase the number and survival of retinal ganglia cells by approximately 54% in 3-month-old C57BL/6 mice (intraperitoneal injection, 50 mg/kg). In addition, mdivi-1 treatment did not affect the increase of Drp1 protein expression, but obviously down-regulate the expression of GFAP[6].
Multiple roles of mdivi-1, such as reduces animal blood pressure, alleviate traumatic brain injury induced brain damage[7], and protect against doxorubicin-induced cardiotoxicity, have confirmed by relevant experiments[8]. In general, mdivi-1 provides a new treatment for stroke, myocardial infarction and neurodegenerative diseases.
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