Mdivi-1 是选择性的发动蛋白相关蛋白 1 (Drp1) 抑制剂。Mdivi-1 是一种有效的线粒体分裂/线粒体自噬抑制剂。

Mdivi-1 is a selective cell-permeable inhibitor of mitochondrial division DRP1 (dynamin-related GTPase) and mitochondrial division Dynamin I (Dnm1) (IC50: 1-10 μM).

在节细胞层,Mdivi-1具有强烈的免疫反应性.在缺血诱导12小时后的GCL中,Mdivi-1可使蛋白表达增加.Mdivi-1使GFAP蛋白表达显著降低,并但不改变Drp1蛋白表达.在正常的小鼠视网膜中,Mdivi-1主要分布在内网层、节细胞层、外网层及内核层.在缺血小鼠视网膜中的早期神经发育中,Mdivi-1和胶质纤维酸性蛋白的蛋白表达会明显增加.Mdivi-1可阻断缺血视网膜中的细胞凋亡,并使缺血两周后的RGC存活率显著增加.

Mdivi-1通过变构调节阻断了Dnm1的ATP酶活性和自组装（IC50<10 μM）。在HeLa细胞和细胞外鼠源肝细胞线粒体配置液中,Mdivi-1有效地抑制了C8-Bid和STS诱导的MOMP（线粒体外膜通透性增加）。Mdivi-1抑制酵母Dnm1和人源Drp1分裂DRPs(发动蛋白相关GTP酶),且高效可逆地诱导线粒体融合进一个巢样的结构。在细胞中,Mdivi-1通过抑制线粒体外膜通透性从而抑制细胞凋亡。Mdivi-1大体上代表了一类治疗中风、心肌梗死和神经退行性疾病的疗法。

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.

Mdivi-1 is dissolved in DMSO. 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.

338967-87-6

C15H10Cl2N2O2S

353.22

Mitochondrial division inhibitor 1

DMSO:35.3 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years