KU-60019

製品コードS1570 バッチS157011

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₀H₃₃N₃O₅S

分子量

547.67

CAS No.

925701-49-1

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

100 mg/mL (182.59 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

5.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in 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. ^[1]
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. ^[2]
特徴	Improved analog of KU-55933, and is more effective at blocking ATM-mediated DDR events.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	U87 and U1242
	濃度	Dissolved in water, final concentrations ~3 μM
	反応時間	1, 3, and 5 days
	実験の流れ	Cells are exposed to KU-60019 for 1, 3, and 5 days. Cell growth is determined by AlamarBlue. AlamarBlue is added to the medium to the recommended final concentration. Plates are incubated for 1 hour at 37 °C, fluorescence is determined on a Fluoro-Count plate reader (excitation 530 nm, emission 590 nm), and values are taken as a measure of cell growth. Cell survival is determined by trypan blue/fluorescence activated cell sorting (FACS) assay.
動物実験	動物モデル	Athymic female mice harboring orthotopic glioma U1242/luc-GFP tumors or human glioma U1242/luc-GFP tumors
	投薬量	KU-60019 (10 μM) is delivered at a rate of 0.5 μL/h by osmotic pump; KU-60019 (250 μM) in 12.5 μL is infused by CED.
	投与方法	Administered intratumorally by convection-enhanced delivery or osmotic pump

参考

カスタマーフィードバック

: Data from [Brain Pathol, 2012, 22(5), 677-88]

: Data from [Data independently produced by , , Brain Pathol, 2012, 22(5): 677-88 ]

: Data from [Data independently produced by , , Brain Pathol, 2012, 22(5): 677-88 ]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Pre-rRNA Facilitates TopBP1-Mediated DNA Double-Strand Break Response [ Adv Sci (Weinh), 2023, 10(28):e2206931]	PubMed: 37582658
Inhibition of CDK12 elevates cancer cell dependence on P-TEFb by stimulation of RNA polymerase II pause release [ Nucleic Acids Res, 2023, 51(20):10970-10991]	PubMed: 37811895
ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias [ Blood Cancer J, 2023, 13(1):42]	PubMed: 36959186
Combination Therapies with CDK4/6 Inhibitors to Treat KRAS-Mutant Pancreatic Cancer [ Cancer Res, 2023, 83(1):141-157]	PubMed: 36346366
Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity [ Int J Biol Sci, 2023, 19(3):981-993]	PubMed: 36778120
Galectin-9 blockade synergizes with ATM inhibition to induce potent anti-tumor immunity [ Int J Biol Sci, 2023, 19(3):981-993]	PubMed: 36778120
A new scaffold-free tumoroid model provides a robust preclinical tool to investigate invasion and drug response in Renal Cell Carcinoma [ Cell Death Dis, 2023, 14(9):622]	PubMed: 37736770
Ribonucleotide reductase subunit switching in hepatoblastoma drug response and relapse [ Commun Biol, 2023, 6(1):249]	PubMed: 36882565
Suppression of TREX1 deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response [ iScience, 2023, 26(7):107090]	PubMed: 37416470
Atypical genotoxicity of carcinogenic nickel(II): Linkage to dNTP biosynthesis, DNA-incorporated rNMPs, and impaired repair of TOP1-DNA crosslinks [ J Biol Chem, 2023, 10.1016/j.jbc.2023.105385]	PubMed: 37890780

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。