VX-984 (M9831) 是一种口服有效、选择性的、可透过血脑屏障的
DNA-PK抑制剂。VX-984 有效抑制 NHEJ (非同源性末端接合)，增加DSBs (DNA 双链断裂)。VX-984 可用于胶质母细胞瘤 (GBM) 和非小细胞肺癌 (NSCLC) 的研究。
| 生物活性 |
VX-984 (M9831) is an orally active, potent, selective and BBB-penetratedDNA-PKinhibitor. VX-984 efficiently inhibits NHEJ (non-homologous end joining) and increases DSBs (DNA double-strand breaks). VX-984 can be used for glioblastomas (GBM) and non-small cell lungcancer(NSCLC) research[1][2][3].
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体外研究
(In Vitro) |
VX-984 (0-500 nM, 30 min) inhibits radiation-induced DNA-PKcs phosphorylation in U251 and NSC11 cells[1].
VX-984 (0-500 nM) enhances the radiosensitivity of U251 and NSC11 cells in a concentration-dependent manner[1].
VX-984 inhibits the repair of radiation-induced DNA double-strand breaks (DSBs)[1].
VX-984 (0-1 μM) increases alternate pathways of DSB repair, including HR (homologous recombination) and mutagenic NHEJ (mNHEJ)[2].
Western Blot Analysis[1]
| Cell Line: |
U251 and NSC11 cells |
| Concentration: |
0, 100, 250, and 500 nM |
| Incubation Time: |
30 min |
| Result: |
Showed a concentration-dependent decrease in radiation-induced DNA-PKcs phosphorylation in each glioma line, when VX-984 was delivered 1 hour before irradiation. VX-984 treatment alone had no effect. |
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体内研究
(In Vivo) |
VX-984 (0-100 mg/kg, Oral gavage, daily) inhibits radiation-induced DNA-PKcs phosphorylation in orthotopic brain tumor xenografts[1].
VX-984 (0-50 mg/kg, Oral gavage, twice a day for 2 days) enhances the radiosensitivity of brain tumor xenografts[1].
| Animal Model: |
Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)[1] |
| Dosage: |
0, 50, and 100 mg/kg |
| Administration: |
Oral gavage, daily, 1 or 4 hours before irradiation (10 Gy) |
| Result: |
Reduced the levels DNA-PKcs phosphorylation after irradiation. |
| Animal Model: |
Athymic female nude mice (6-8 weeks old, 7 mice/group, U251 intracerebral xenografts)[1] |
| Dosage: |
0, 50 mg/kg |
| Administration: |
Oral gavage, twice a day, 30 minutes before and 4 hours following local irradiation of the tumor (3 Gy) for 3 consecutive days (3×3 Gy) |
| Result: |
VX-984 treatment of U251 tumors alone had no significant effect on overall survival as compared with vehicle; radiation alone resulted in an increase in survival. VX-984 and radiation combination protocol increased tumor radiosensitivity, and significantly increased the survival of mice compared with radiation alone. |
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| Clinical Trial |
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| 分子量 |
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| 性状 |
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| Formula |
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| CAS 号 |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
| Powder |
-20°C |
3 years |
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4°C |
2 years |
| In solvent |
-80°C |
6 months |
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-20°C |
1 month |
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| 溶解性数据 |
In Vitro:
DMSO : 10 mg/mL(24.07 mM;Need ultrasonic)
配制储备液
| 1 mM |
2.4068 mL |
12.0340 mL |
24.0680 mL |
| 5 mM |
0.4814 mL |
2.4068 mL |
4.8136 mL |
| 10 mM |
0.2407 mL |
1.2034 mL |
2.4068 mL |
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请根据半岛bd体育手机客户端 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半岛bd体育手机客户端 失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶
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1.
请依序添加每种溶剂： 10% DMSO40%PEG3005%Tween-8045% saline
Solubility: ≥ 1 mg/mL (2.41 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (2.41 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
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2.
请依序添加每种溶剂： 10% DMSO90%corn oil
Solubility: ≥ 1 mg/mL (2.41 mM); Clear solution
此方案可获得 ≥ 1 mg/mL (2.41 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
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以上所有助溶剂都可在本网站选购。
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