Mdivi 1
(Synonyms: 3-(2,4-二氯-5-甲氧基苯基)-2,3-二氢-2-硫代-4(1H)-喹唑啉酮,Mitochondrial division inhibitor 1) 目录号 : GC10200
Mdivi-1（线粒体分裂抑制剂 1）抑制创伤性脑损伤 (TBI) 诱导的动力蛋白相关蛋白 1 (Drp1) 上调、自噬功能障碍和线粒体自噬激活。
Cas No.:338967-87-6
Sample solution is provided at 25 µL, 10mM.
Mdivi-1 (Mitochondrial division inhibitor 1) inhibits traumatic brain injury (TBI)-induced dynamin-related protein 1(Drp1) up-regulation, autophagy dysfunction and mitophagy activation. Mdivi-1 decreased TBI-induced cell death and lesion volume [1,2].
Mdivi-1 is a selective Drp 1 inhibitor with IC50 value as 10 mμ[3]. Mdivi-1 significantly alleviated the scratch injury-induced cell death, loss of mitochondrial membrane potential, reactive oxygen species (ROS) production and ATP reduction in primary cortical neurons (PCNs). Additionally, the lysosome inhibitor chloroquine (CQ) abrogated the Mdivi-1-induced decrease in autophagosomes accumulation and cell death at 24 h both in the basal state and under the conditions of scratch cell injury [1].
Mdivi-1 could significantly rescue neurons from death induced by seizures in a dose-dependent manner. In addition, the seizures increase Drp1 expression in hippocampus. These suggested that the up-regulation of Drp1 expression could be partially responsible for seizure-induced neuronal death. Moreover, CytC release, AIF translocation and caspase-3 activation may be involved in the protective mechanisms of mdivi-1 against seizure-induced neuronal death [4].
References:
[1]. Q. Wu, C. Gao, H. Wang, X. Zhang, et al. Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation. Int. J. Biochem. Cell Biol., 94 (2018), pp. 44-55, 10.1016/j.biocel.2017.11.007
[2]. Q. Wu, S.X. Xia, Q.Q. Li, et al. Mitochondrial division inhibitor 1 (Mdivi-1) offers neuroprotection through diminishing cell death and improving functional outcome in a mouse model of traumatic brain injury. Brain Res., 1630 (2016), pp. 134-143
[3]. D. Wu, A. Dasgupta, K.H. Chen, M. Neuber-Hess, J. Patel, T.E. Hurst, J.D. Mewburn, P.D.A. Lima, E. Alizadeh, A. Martin, M. Wells, V. Snieckus, S.L. Archer. Identification of novel dynamin-related protein 1 (Drp1) GTPase inhibitors: therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia-reperfusion injury.FASEB J., 34 (2020), pp. 1447-1464
[4]. Xie N, Wang C, Lian Y, Zhang H, Wu C, Zhang Q. A selective inhibitor of Drp1, mdivi-1, protects against cell death of hippocampal neurons in pilocarpine-induced seizures in rats. (2013b) Neurosci Lett 545: 64 -68.
Mdivi-1（线粒体分裂抑制剂 1）抑制创伤性脑损伤 (TBI) 诱导的动力蛋白相关蛋白 1 (Drp1) 上调、自噬功能障碍和线粒体自噬激活。 Mdivi-1 减少了 TBI 诱导的细胞死亡和损伤体积 [1,2]。
Mdivi-1 是一种选择性 Drp 1 抑制剂，IC50 值为 10 mμ[3]。 Mdivi-1 显着减轻了划痕损伤引起的细胞死亡、线粒体膜电位丧失、活性氧 (ROS) 产生和原代皮层神经元 (PCN) 中 ATP 的减少。此外，在基础状态和划痕细胞损伤条件下，溶酶体抑制剂氯喹 (CQ) 在 24 小时内消除了 Mdivi-1 诱导的自噬体积累减少和细胞死亡[1]。
Mdivi-1 可以剂量依赖性方式显着挽救神经元免于癫痫发作引起的死亡。此外，癫痫发作会增加海马体中 Drp1 的表达。这些表明 Drp1 表达的上调可能是癫痫发作引起的神经元死亡的部分原因。此外，CytC释放、AIF易位和caspase-3激活可能参与了mdivi-1对癫痫引起的神经元死亡的保护机制[4]。
| Cell experiment [1]: | |
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Cell lines |
Primary cortical neuron(PCN) |
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Preparation Method |
PCNs were treated with Mdivi-1 (from 0.001 nM to 1 mM) dissolved in 0.1% DMSO 1 h before scratch cell injury. The release of lactate dehydrogenase(LDH)into the culture media was measured 6 h after scratch cell injury. |
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Reaction Conditions |
0.001 nM to 1 mM for 1hour |
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Applications |
Using LDH assay, exposing PCNs to scratch cell injury with Mdivi-1 (100 µM and 1 mM) resulted in significant dose-dependent inhibition of cell death. Hence the range of the optimum concentration was from 10 µM to 100 µM. |
| Animal experiment [2]: | |
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Animal models |
male ICR mice |
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Preparation Method |
For the mice treated with Mdivi-1 (3 mg/kg), dynamin-related protein 1 (Drp1) inhibitor, was administered by intraperitoneal injection 10 min after TBI. Mdivi-1 was dissolved in 0.01 M PBS. Vehicle animals received an intraperitoneal injection of 0.01 M PBS. |
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Dosage form |
Intraperitoneal injection, 3 mg/kg |
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Applications |
Treatment with Mdivi-1 accelerated the recovery of motor functional outcome on days 3-5 post-TBI. After injury, animals subjected to Mdivi-1 treatment demonstrated a significant decrease in the latencies, relative to vehicle mice on days 15 and 16, thereby Mdivi-1 treatment could result in cognitive functional recovery. |
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References: [1]: Q. Wu, C. Gao, H. Wang, X. Zhang, et al. Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation. Int. J. Biochem. Cell Biol., 94 (2018), pp. 44-55, 10.1016/j.biocel.2017.11.007 |
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| Cas No. | 338967-87-6 | SDF | |
| 别名 | 3-(2,4-二氯-5-甲氧基苯基)-2,3-二氢-2-硫代-4(1H)-喹唑啉酮,Mitochondrial division inhibitor 1 | ||
| 化学名 | 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanylidene-1H-quinazolin-4-one | ||
| Canonical SMILES | COC1=C(C=C(C(=C1)N2C(=O)C3=CC=CC=C3NC2=S)Cl)Cl | ||
| 分子式 | C15H10Cl2N2O2S | 分子量 | 353.22 |
| 溶解度 | ≥ 17.65mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8311 mL | 14.1555 mL | 28.311 mL |
| 5 mM | 0.5662 mL | 2.8311 mL | 5.6622 mL |
| 10 mM | 0.2831 mL | 1.4155 mL | 2.8311 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Mdivi-1 (Lot: GC10200) was bought from Glpbio (USA).
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