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]. |
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. |
|
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. |
|
| Clinical Trial | |
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
| 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 |
*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℃, 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 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% 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。 2. 请依序添加每种溶剂： 10% DMSO 90%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。 *以上所有助溶剂都可在本网站选购。
|
