VBIT-4
目录号 : GC39167
VBIT-4是电压依赖性阴离子通道1（VDAC1）寡聚化的抑制剂，对纯化VDAC1的Kd值为3μM。
Cas No.:2086257-77-2
Sample solution is provided at 25 µL, 10mM.
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VBIT-4 is an inhibitor of voltage-dependent anion channel 1 (VDAC1) oligomerization, with a Kd value of 3μM for purified VDAC1 [1]. VBIT-4 induces depolarization of organelles fueled by substrates of complex I of the respiratory chain and suppresses mitochondrial dysfunction by preventing VDAC1 oligomerization [2]. VBIT-4 has been widely used in cell models to regulate mitochondrial function and oxidative stress[3].
In vitro, VBIT-4 (15μM) pretreatment for 2 hours significantly inhibited the apoptosis and mitochondrial cytochrome c release induced by staurosporine (0.2μM; 3h)[4]. Treatment with 10μM VBIT-4 for 24 hours significantly inhibited the accumulation of mitochondrial ROS, total lipid peroxide, and mitochondrial lipid peroxide in SK-Hep1 cells induced by Erastin, and suppressed ferroptosis[5].
In vivo, VBIT-4 treatment via intraperitoneal injection (20mg/kg) every other day for 4 weeks can reduce mitochondrial calcium overload in the skeletal muscles of D2.DMDel8-34 mice, enhance the resistance to permeability transition pore-induced stimuli, and improve the ultrastructure of mitochondria[6]. Oral administration of 20mg/kg dose of VBIT-4 daily for 5 months inhibited neuronal death, neuroinflammation and neuro-metabolic dysfunction in 5×FAD mice, and prevented cognitive decline[7].
References:
[1] Gorny H, Mularoni A, Delcros J G, et al. Combining nano-differential scanning fluorimetry and microscale thermophoresis to investigate VDAC1 interaction with small molecules[J]. Journal of enzyme inhibition and medicinal chemistry, 2023, 38(1): 2121821.
[2] Belosludtsev K N, Ilzorkina A I, Matveeva L A, et al. Effect of VBIT-4 on the functional activity of isolated mitochondria and cell viability[J]. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2024, 1866(5): 184329.
[3] Miura S, Sekine T, Okochi S, et al. Exacerbation of Doxorubicin-Induced Mitochondrial Dysfunction by the Inhibition of Voltage-Dependent Anion Channel 1 Oligomerization[J]. Circulation, 2025, 152(Suppl_3): A4361657-A4361657.
[4] Ben-Hail D, Begas-Shvartz R, Shalev M, et al. Novel compounds targeting the mitochondrial protein VDAC1 inhibit apoptosis and protect against mitochondrial dysfunction[J]. Journal of Biological Chemistry, 2016, 291(48): 24986-25003.
[5] Oh S J, Ikeda M, Ide T, et al. Mitochondrial event as an ultimate step in ferroptosis[J]. Cell death discovery, 2022, 8(1): 414.
[6] Dubinin M V, Stepanova A E, Mikheeva I B, et al. VBIT-4 Rescues Mitochondrial Dysfunction and Reduces Skeletal Muscle Degeneration in a Severe Model of Duchenne Muscular Dystrophy[J]. International Journal of Molecular Sciences, 2025, 26(18): 8845.
[7] Verma A, Shteinfer-Kuzmine A, Kamenetsky N, et al. Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer’s disease protects against mitochondrial dysfunction and mitigates brain pathology[J]. Translational Neurodegeneration, 2022, 11(1): 58.
VBIT-4是电压依赖性阴离子通道1（VDAC1）寡聚化的抑制剂，对纯化VDAC1的Kd值为3μM[1]。VBIT-4能诱导呼吸链复合物I底物驱动的细胞器去极化，并通过阻止VDAC1寡聚化来抑制线粒体功能障碍[2]。VBIT-4已广泛应用于细胞模型中，用于调节线粒体功能和氧化应激[3]。
在体外，VBIT-4（15μM）预处理2小时显著抑制了staurosporine（0.2μM；3小时）诱导的细胞凋亡和线粒体细胞色素c释放[4]。用10μM的VBIT-4处理24小时显著抑制了Erastin诱导的SK-Hep1细胞中线粒体ROS、总脂质过氧化物和线粒体脂质过氧化物的积累，并抑制了铁死亡[5]。
在体内，VBIT-4通过腹腔注射（20mg/kg）每隔一天治疗4周，可以减少D2.DMDel8-34小鼠骨骼肌中的线粒体钙超载，增强对通透性转换孔诱导刺激的抵抗力，并改善线粒体的超微结构[6]。每日口服20mg/kg剂量的VBIT-4连续5个月，可抑制5×FAD小鼠的神经元死亡、神经炎症和神经代谢功能障碍，并防止认知能力下降[7]。
| Cell experiment [1]: | |
Cell lines | SK-Hep1 cells |
Preparation Method | SK-Hep1 cells were cultured in DMEM medium supplemented with 1% penicillin-streptomycin-azithromycin mixture and 10% fetal bovine serum, maintained in a 5% CO2 atmosphere at 37°C. A total of 1×104 cells were seeded in a 96-well plate and exposed to 10μM VBIT-4 and 5μM Erastin for 24 hours. The supernatant was then collected for lactate dehydrogenase (LDH) analysis to assess cell death. |
Reaction Conditions | 10μM; 24h |
Applications | VBIT-4 treatment almost completely abrogated Erastin-induced SK-Hep1 cell death. |
| Animal experiment [2]: | |
Animal models | Male 5×FAD transgenic mice |
Preparation Method | Male 5×FAD transgenic mice were housed in groups of 4, with a light/dark cycle of 12/12 hours, and had free access to food and water. VBIT-4 was dissolved in DMSO (80mg/ml), and then diluted with drinking water to an ultimate concentration of 0.0625mg/ml, and the daily intake dose was 20mg/kg (n=9). The untreated 5×FAD mice (n=8) in the control group drank water containing 0.36% DMSO. After 5 months of treatment, the brain tissues of the mice were collected for analysis. |
Dosage form | 20mg/kg/day for 5 months; p.o. |
Applications | VBIT-4 treatment reduced the level of Aβ plaques in the brain tissue of 5×FAD mice and prevented neuronal loss. |
References: | |
| Cas No. | 2086257-77-2 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C(Cl)C=C1)CC(CO)N2CCN(C3=CC=C(OC(F)(F)F)C=C3)CC2 | ||
| 分子式 | C21H23ClF3N3O3 | 分子量 | 457.87 |
| 溶解度 | DMSO: 125 mg/mL (273.00 mM) | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.184 mL | 10.9201 mL | 21.8403 mL |
| 5 mM | 436.8 μL | 2.184 mL | 4.3681 mL |
| 10 mM | 218.4 μL | 1.092 mL | 2.184 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 |
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| % 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.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet