产品说明书

KU-60019

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Chemical Structure| 925701-46-8 同义名 : -
CAS号 : 925701-46-8
货号 : A231772
分子式 : C30H33N3O5S
纯度 : 99+%
分子量 : 547.665
MDL号 : MFCD18384974
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(191.72 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 8 mg/mL(14.61 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 4 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
描述 The serine/threonine protein kinase ATM signals can regulate cell cycle and DNA repair components through phosphorylation on the targets such as p53, CHK2, NBS1, and BRCA1, thus playing a central role in the maintenance of genome integrity. KU-60019 is an improved inhibitor of the ATM kinase (compared with KU-55933) with an IC50 of 6.3 nM. Pre-treatment with KU-60019 can inhibit the downstream targets p53 phosphorylation at Ser15 site, as well as CHK2 at T68 site, induced by 5Gy of ionizing radiation in U1242 cells. Compared with KU-55933, KU-60019 acts as a more potent radiosensitizer at concentration>1 μM in U87 and U1242 human glioma cells but not A-T fibroblasts. Treatment with KU-60019 resulted in inhibited migration of U87 cells ≥70% in a dose-dependent manner and inhibited invasion of U1242 cells by ∼60%, which may due to the impaired AKT signaling[1]. In in vivo study, combination of radiation and KU-60019 administrated by pump implantation at dose of 10μM, significantly increase survival of mice 2- to 3-fold over controls in orthotopic human glioma xenograft models[2].
作用机制 KU-60019 is an improved form of KU-55933, which is an ATP-competitive ATM inhibitor.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
BAECs 10 μM Function Assay 1 h  abolishes the phosphorylation of ATM-Ser1981 25498542
BAECs 10 μM Function Assay 1 h  inhibits the increase in NOS activity 25498542
U1242 3 μM  Kinase Assay 0.5 h  inhibits the ATM kinase 23620409
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.83mL

0.37mL

0.18mL

9.13mL

1.83mL

0.91mL

18.26mL

3.65mL

1.83mL
参考文献

[1]Golding SE, Rosenberg E, et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902.

[2]Biddlestone-Thorpe L, Sajjad M, et al. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res. 2013 Jun 15;19(12):3189-200.