AZD-7648 是一种具有选择性的口服有效DNA-PK抑制剂，IC50值为 0.6 nM, AZD-7648 诱导细胞凋亡 (apoptosis)，具有抗肿瘤活性。
| 生物活性 | AZD-7648 is a potent, orally active, selectiveDNA-PKinhibitor with anIC50of 0.6 nM. AZD-7648 inducesapoptosisand shows antitumor activity[1]. |
| IC50& Target | DNA-PKcs 91.3 nM (IC50) | PI3Kγ 1.37 μM (IC50) | ATM 17.93 μM (IC50) |
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体外研究
(In Vitro) | AZD7648 (0-30 μM) is a potent radiosensitizer[1].
AZD7648 (3 μM) increases sensitivity to doxorubicin[1].
AZD7648 (0.6 μM) enhances the activity of PARP inhibitor olaparib[1].
Western Blot Analysis[1] | Cell Line: | IR (ionizing radiation)-treated A549 cells or OAW42 cells treated with doxorubicin | | Concentration: | 0.03, 0.1, 0.3, 1, 3, 10 and 30 μM for A549; 3 μM for OAW42 | | Incubation Time: | 1 h for A549; 0.5, 2, 4, 8 and 16 h for OAW42 | | Result: | Potently inhibited DNA-PKcs autophosphorylation at Ser2056. Downregulated pDNA-PKcs Ser2056, γH2AX Ser139 and pRPA32 Ser4/Ser8 phosphorylation at early time points (at 30 min, 2 h and 4 h). Resulted in increased levels of γH2AX and the apoptosis marker cleaved PARP1 compared with doxorubicin treatment alone at later time points (8 and 16 h). |
Cell Cycle Analysis[1] | Cell Line: | IR (ionizing radiation)-treated A549 cells or A549 cells | | Concentration: | 0-30 μM | | Incubation Time: | 48 h | | Result: | Arrested cell cycle at G2/M phase. |
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体内研究
(In Vivo) | AZD-7648 (100 mg/kg; p.o.; once daily for 5 days) induces tumour growth inhibition and tumour regression[1].
| Animal Model: | Nude mice, A549 xenografts and NCI-H1299 xenografts[1] | | Dosage: | 100 mg/kg | | Administration: | Oral administration, once daily for 5 days | | Result: | Induced tumour growth inhibition in combination with IR in A549 xenografts and induced tumour regression in combination with IR in NCI-H1299 xenografts. |
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| 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 |
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| 溶解性数据 | In Vitro: DMSO : 5 mg/mL(13.14 mM;ultrasonic and warming and heat to 80℃) 配制储备液 | 1 mM | 2.6288 mL | 13.1441 mL | 26.2881 mL | | 5 mM | 0.5258 mL | 2.6288 mL | 5.2576 mL | | 10 mM | 0.2629 mL | 1.3144 mL | 2.6288 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： 0.5% HPMC 0.1%Tween80 Solubility: 10 mg/mL (26.29 mM); Suspended solution; Need ultrasonic
*以上所有助溶剂都可在本网站选购。 |
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