计算溶液所需的质量、体积或浓度。
| 活性类型 | 活性值-log(M) | 作用机制 | 期刊 | 参考文献(PubMed IDs) |
|---|
KU-60019, ATM 丝氨酸/苏氨酸激酶抑制剂
有货
为什么选择此级别
Moligand™ 级 ，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
-80℃储存。特低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
概述
KU-60019是KU-55933的改良类似物，对ATM的IC50为6.3 nM。
Information
KU-60019 is an improved analogue of KU-55933, withIC50of 6.3 nM forATMin cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.
In vitro
Compared to KU-55933, KU-60019 is an improved inhibitor of the ATM kinase, while displaying similar target selectivity. KU-60019 has little activity against DNA-PKcs and ATR with IC50 values of 1.7 μM and >10 μM, respectively, as well as 229 other protein kinases such as PI3K, mTOR and mTOR/FKBP12. KU-60019 displays 3- to 10-fold more potency than KU-55933 at blocking radiation-induced phosphorylation of key ATM protein targets such as p53, γ-H2AX, and CHK2, in human glioma U87 and U1242 cells, as 1 μM of KU-60019 significantly induces >70% decrease of p53 (S15) phosphorylation to which extent ~10 μM of KU-55933 is required to achieve. KU-60019 effectively radiosensitizes human glioma cells with dose-enhancement ratio of 1.7 and 4.4 at 1 μM and 10 μM, respectively, and also radiosensitizes the normal fibroblasts but not the A-T fibroblasts. KU-60019 treatment (3 μM) blocks basal and insulin-induced AKT S473 phosphorylation by 70% and ~50%, respectively, and completely reduces radiation-induced AKT phosphorylation below the level of control. The effect of KU-60019 on AKT S473 phosphorylation can be seen in glioma cell lines and normal fibroblasts but not in A-T (h-TERT) cells, and can be significantly blocked by phosphatase inhibitor okadaic acid, suggesting a critical role of ATM kinase in regulating AKT phosphorylation via unknown phosphatase. Consistent with the inhibition of prosurvival AKT signaling, KU-60019 at 3 μM significantly inhibits migration and invasion of human glioma U87 cells by >70% and ~60%, respectively, as well as U1242 cells by >50% and ~60% respectively.
In vivo
In orthotopic glioma U1242/luc-GFP xenograft models, the combination of KU-60019 and radiation significantly increases survival of mice than KU-60019 alone, radiation alone, or no treatment. In addition, p53-mutant gliomas is much more sensitive to KU-60019 radiosensitization than wild-type glioma.
Cell Data
cell lines：
Concentrations：Dissolved in water, final concentrations ~3 μM
Incubation Time：1, 3, and 5 days
Powder Purity:≥97%
规格
英文别名
2-((2S,6R)-2,6-dimethylmorpholino)-N-(5-(6-morpholino-4-oxo-4H-pyran-2-yl)-9H-thioxanthen-2-yl)acetamide
规格或纯度
Moligand™, 10mM in DMSO
英文名称
KU-60019
生化机理
KU-60019 是 KU-55933 的改进类似物，在无细胞实验中对 ATM 的 IC50 值为 6.3 nM，对 ATM 的选择性分别是 DNA-PK 和 ATR 的 270 倍和 1600 倍，是一种高效的放射增敏剂。
储存条件
-80℃储存
运输条件
特低温运输
作用类型
抑制剂
作用机制
ATM 丝氨酸/苏氨酸激酶抑制剂
名称和识别符
分子类型
小分子
Isomeric SMILES
C[C@@H]1CN(C[C@@H](O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C3)C=CC=C4C5=CC(=O)C=C(O5)N6CCOCC6
分子量
547.68
Reaxy-Rn
15466363
Reaxys-RN link address
https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=15466363&ln=
技术文档
高级数据
关联靶点（人）
PIK3C3
Tchem
磷脂酰肌醇3-激酶催化亚基3型(Phosphatidylinositol 3-kinase catalytic subunit type 3)
(2 活性数据)
ATM
Tchem
丝氨酸蛋白激酶 ATM(Serine-protein kinase ATM)
(4 活性数据)
化学和物理性质
溶解性
Solubility (25°C) In vitro DMSO: 55 mg/mL (197.06 mM); Water: 55 mg/mL (197.06 mM); Ethanol: 55 mg/mL (197.06 mM);
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
输入批号以搜索分析图谱:
溶液计算器
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