MitoBloCK-6
目录号 : GC68213MitoBloCK-6 是一种有效的 Erv1/ALR 抑制剂，IC50 分别为 900 nM 和 700 nM。MitoBloCK-6 还抑制 Erv2 (IC50=1.4 μM)。MitoBloCK-6 可通过细胞色素 c 的释放诱导 hESCs 细胞凋亡。
Cas No.:303215-67-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
IC50: 900 nM (Erv1) 700 nM (ALR) 1.4 μM (Erv2)[1]
MitoBloCK-6 is a potent Erv1/ALR inhibitor, with an IC50 of 900 nM and 700 nM, respectively. MitoBloCK-6 also inhibits Erv2 (IC50=1.4 μM). MitoBloCK-6 can induce Apoptosis via cytochrome c release in hESCs[1].
[1]. Dabir DV, et, al. A small molecule inhibitor of redox-regulated protein translocation into mitochondria. Dev Cell. 2013 Apr 15;25(1):81-92.
| Cas No. | 303215-67-0 | SDF | Download SDF |
| 分子式 | C19H14Cl2N2O | 分子量 | 357.23 |
| 溶解度 | DMSO : 50 mg/mL (139.97 mM; Need ultrasonic and warming) | 储存条件 | 4°C, protect from light |
| 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 | 2.7993 mL | 13.9966 mL | 27.9932 mL |
| 5 mM | 0.5599 mL | 2.7993 mL | 5.5986 mL |
| 10 mM | 0.2799 mL | 1.3997 mL | 2.7993 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。
Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation
Front Cell Dev Biol 2021 Sep 20;9:725474.PMID:34616733DOI:10.3389/fcell.2021.725474.
Augmenter of liver regeneration (ALR) is a critical multi-isoform protein with its longer isoform, located in the mitochondrial intermembrane space, being part of the mitochondrial disulfide relay system (DRS). Upregulation of ALR was observed in multiple forms of cancer, among them hepatocellular carcinoma (HCC). To shed light into ALR function in HCC, we used MitoBloCK-6 to pharmacologically inhibit ALR, resulting in profound mitochondrial impairment and cancer cell proliferation deficits. These effects were mostly reversed by supplementation with bioavailable hemin b, linking ALR function to mitochondrial iron homeostasis. Since many tumor cells are known for their increased iron demand and since increased iron levels in cancer are associated with poor clinical outcome, these results help to further advance the intricate relation between iron and mitochondrial homeostasis in liver cancer.
A small molecule inhibitor of redox-regulated protein translocation into mitochondria
Dev Cell 2013 Apr 15;25(1):81-92.PMID:23597483DOI:10.1016/j.devcel.2013.03.006.
The mitochondrial disulfide relay system of Mia40 and Erv1/ALR facilitates import of the small translocase of the inner membrane (Tim) proteins and cysteine-rich proteins. A chemical screen identified small molecules that inhibit Erv1 oxidase activity, thereby facilitating dissection of the disulfide relay system in yeast and vertebrate mitochondria. One molecule, mitochondrial protein import blockers from the Carla Koehler laboratory (MitoBloCK-6), attenuated the import of Erv1 substrates into yeast mitochondria and inhibited oxidation of Tim13 and Cmc1 in in vitro reconstitution assays. In addition, MitoBloCK-6 revealed an unexpected role for Erv1 in the carrier import pathway, namely transferring substrates from the translocase of the outer membrane complex onto the small Tim complexes. Cardiac development was impaired in MitoBloCK-6-exposed zebrafish embryos. Finally, MitoBloCK-6 induced apoptosis via cytochrome c release in human embryonic stem cells (hESCs) but not in differentiated cells, suggesting an important role for ALR in hESC homeostasis.
Carbon starvation, senescence and specific mitochondrial stresses, but not nitrogen starvation and general stresses, are major triggers for mitophagy in Arabidopsis
Autophagy 2022 Dec;18(12):2894-2912.PMID:35311445DOI:10.1080/15548627.2022.2054039.
Selective degradation of mitochondria by autophagy (mitophagy) is thought to play an important role in mitochondrial quality control, but our understanding of which conditions induce mitophagy in plants is limited. Here, we developed novel reporter lines to monitor mitophagy in plants and surveyed the rate of mitophagy under a wide range of stresses and developmental conditions. Especially carbon starvation induced by dark-incubation causes a dramatic increase in mitophagy within a few hours, further increasing as dark-induced senescence progresses. Natural senescence was also a strong trigger of mitophagy, peaking when leaf yellowing became prominent. In contrast, nitrogen starvation, a trigger of general autophagy, does not induce strong increases in mitophagy. Similarly, general stresses such as hydrogen peroxide, heat, UV-B and hypoxia did not appear to trigger substantial mitophagy in plants. Additionally, we exposed plants to inhibitors of the mitochondrial electron transport chain, mitochondrial translation and protein import. Although short-term treatments did not induce high mitophagy rates, longer term exposures to uncoupling agent and inhibitors of mitochondrial protein import/translation could clearly increase mitophagic flux. These findings could further be confirmed using confocal microscopy. To validate that mitophagy is mediated by the autophagy pathway, we showed that mitophagic flux is abolished or strongly decreased in atg5/AuTophaGy 5 and atg11 mutants, respectively. Finally, we observed high rates of mitophagy in etiolated seedlings, which remarkably was completely repressed within 6 h after light exposure. In conclusion, we propose that dark-induced carbon starvation, natural senescence and specific mitochondrial stresses are key triggers of mitophagy in plants.Abbreviations: AA: antimycin A; ATG: AuToPhagy related; ConA: concanamycin A; DIS: dark-induced senescence; Dox: doxycycline; FCCP: carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; GFP: green fluorescent protein; IDH1: isocitrate dehydrogenase 1; MB: MitoBloCK-6; Mito-GFP: transgenic Arabidopsis line expressing a mitochondrially targeted protein fused to GFP; mtETC: mitochondrial electron transport chain; OXPHOS: oxidative phosphorylation; PQC: protein quality control; TOM20: Translocase of Outer Membrane 20.