VX-984 M9831|cas:1476074-39-1|西域试剂

VX-984 M9831,99.20%

产品编号：Bellancom-19939S| CAS NO：1476074-39-1| 分子式：C₂₃H₂₁D₂N₇O| 分子量：415.49

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-19939S	￥6500.00	杭州北京（现货）
Bellancom-19939S	￥11000.00	杭州北京（现货）
Bellancom-19939S	￥45000.00	杭州北京（现货）

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VX-984 M9831

产品介绍

VX-984 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。VX-984 是一种从头设计的氘代物。

生物活性

VX-984 is an orally active, potent, selective and BBB-penetrated DNA-PK inhibitor. 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 lung cancer (NSCLC) research. VX-984 is a de novo deuterium.

体外研究

VX-984 (0-500 nM，30 分钟) 抑制 U251 和 NSC11 细胞中辐射诱导的 DNA-PKcs 磷酸化。
VX-984 (0-500 nM) 以浓度依赖性方式增强 U251 和 NSC11 细胞的放射敏感性。
VX-984 抑制辐射诱导的 DNA 双链断裂 (DSB) 的修复。
VX-984 (0-1 μM) 增加 DSB 修复的替代途径，包括 HR（同源重组）和诱变 NHEJ (mNHEJ)。
氢、碳和其他元素的稳定重同位素已被掺入药物分子中，主要用作药物开发过程中定量的示踪剂。氘代因其可能影响药物的药代动力学和代谢特征而受到关注^[4]。
氘代化合物的潜在优势：
(1) 延长体内半衰期。氘代化合物可能能够延长化合物的药代动力学特征，即延长体内半衰期。这可以提高化合物的安全性、功效和耐受性，并增加给药的便利性。
(2)提高口服生物利用度。氘化化合物可以降低肠壁和肝脏中不需要的代谢（首过代谢）的程度，使更大比例的未代谢药物到达其作用靶点。高生物利用度决定了它在低剂量下的活性和更好的耐受性。
(3)改善代谢特性。氘代化合物可以减少有毒或反应性代谢物的形成并改善药物代谢。
（四）提高用药安全性。氘代化合物可以减少或消除药物化合物的不良副作用并且是安全的。
(5) 保持治疗特性。在先前的研究中，预计氘代化合物将保留与氢类似物相似的生化效力和选择性。

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis

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.
VX-984 (0-50 mg/kg, Oral gavage, twice a day for 2 days) enhances the radiosensitivity of brain tumor xenografts.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)
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)
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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)
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)
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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Athymic female nude mice (6-8 weeks old, 7-8 mice/group, U251 intracerebral xenografts)
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)
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.

性状

Solid

溶解性数据

In Vitro:

DMSO : 10 mg/mL (24.07 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

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°C, 6 months; -20°C, 1 month。-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。

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。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
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。