3-(2,4-二氯-5-甲氧基苯基)-2,3-二氢-2-硫代-4(1H)-喹唑啉酮

• 常用名: 3-(2,4-二氯-5-甲氧基苯基)-2,3-二氢-2-硫代-4(1H)-喹唑啉酮
• 英文名: Mdivi-1
• CAS号: 338967-87-6
• 分子量: 353.223
• 密度: 1.6±0.1 g/cm3
• 沸点: 522.5±60.0 °C at 760 mmHg
• 分子式: C₁₅H₁₀Cl₂N₂O₂S
• 熔点: 289 °C
• 闪点: 269.8±32.9 °C

用途

Mdivi-1是选择性的发动蛋白相关蛋白1 (Drp1) 抑制剂。

名称

• 中文名: 3-(2,4-二氯-5-甲氧基苯基)-2,3-二氢-2-硫代-4(1H)-喹唑啉酮
• 英文名: 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanylidene-1H-quinazolin-4-one

生物活性

• 描述: Mdivi-1是选择性的发动蛋白相关蛋白1 (Drp1) 抑制剂。
• 相关类别:
  信号通路 >> 细胞骨架 >> 动力素
  研究领域 >> 癌症
• 体外研究: Mdivi-1以剂量依赖性方式抑制Dnm1 GTP酶活性,估计EC50为1-10μM。 Mdivi-1增加GTP的表观K0.5,降低GTP水解的表观Vmax,并导致Dnm1 GTP水解反应中观察到的GTP的Hill系数增加[1]。用mdivi-1处理的细胞显示细胞色素c释放减少,细胞凋亡诱导后表面磷脂酰丝氨酸暴露率降低,与细胞凋亡的抑制一致,以及之前的研究使用其他策略来破坏DRP1活性[2]。 Mdivi-1导致缺血性视网膜中的凋亡细胞死亡[3]。
• 体内研究: 线粒体分裂DRP,Dnm1,是体内mdivi-1的靶标。 Mdivi-1定量阻断GMPPCP依赖性Dnm1自组装,其浓度范围与其对体内线粒体分裂的影响相似[1]。 Mdivi-1(50 mg/kg,ip)显着降低正常小鼠视网膜中GFAP蛋白的表达[3]。
• 激酶实验: 所有GTP酶测定反应均在200μL体积中开始，其中将150μL置于96孔板的孔中。通过读取反应的A340监测的NADH的消耗，使用SpectraMAX 250 96孔板读数器每20秒测量总共40分钟。将分光光度数据转移至Excel，并将测得的NADH稳态耗尽随时间转化为蛋白质活性。
• 细胞实验: YPGlycerol板顶部装有10mL含有1％低熔点琼脂和75μMmdivi-1的YP甘油，12小时后使用48孔钉扎装置点样细胞。钉住细胞后，将板在24℃或37℃温育，并使用Eagle Eye II成像系统成像。
• 参考文献:

  [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.

物理化学性质

• 密度: 1.6±0.1 g/cm3
• 沸点: 522.5±60.0 °C at 760 mmHg
• 熔点: 289 °C
• 分子式: C₁₅H₁₀Cl₂N₂O₂S
• 分子量: 353.223
• 闪点: 269.8±32.9 °C
• 精确质量: 351.984009
• PSA: 82.92000
• LogP: 3.85
• InChIKey: NZJKEVWTYMOYOR-UHFFFAOYSA-N
• SMILES: COc1cc(-n2c(=S)[nH]c3ccccc3c2=O)c(Cl)cc1Cl
• 外观性状: 固体;White to Light yellow powder to crystal
• 蒸汽压: 0.0±1.4 mmHg at 25°C
• 折射率: 1.729
• 储存条件: Store at -20°C
• 水溶解性: DMSO: >20mg/mL

安全信息

• 危害码 (欧洲): Xi
• 危险品运输编码: NONH for all modes of transport

靶点实验

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英文别名

• 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