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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (9.13mM)	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. This compound 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. It 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 this inhibitor significantly induces >70% decrease of p53 (S15) phosphorylation to which extent ~10 μM of KU-55933 is required to achieve. This chemical 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. Its 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 this agent 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, it 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 this compound alone, radiation alone, or no treatment. In addition, p53-mutant gliomas is much more sensitive to this chemical 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. This compound 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

https://pubmed.ncbi.nlm.nih.gov/19808981/
https://pubmed.ncbi.nlm.nih.gov/23620409/

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：

Phase separation of ERCC6L2-CtIP regulates the extent of DNA end resection [ Nat Cell Biol, 2025, 27(10):1771-1784]	PubMed: 40913148
R406 and its structural analogs reduce SNCA/α-synuclein levels via autophagic degradation [ Autophagy, 2025, 1-17.]	PubMed: 40143425
Halting hepatocellular carcinoma: Identifying intercellular crosstalk in HBV-driven disease [ Cell Rep, 2025, 44(4):115457]	PubMed: 40163359
Loss of genome maintenance is linked to mTOR complex 1 signaling and accelerates podocyte damage [ JCI Insight, 2025, 10(12)e172370]	PubMed: 40392611
ATR Inhibition Synergizes With Alkylating PI Polyamide Targeting MYCN by Suppressing DNA Repair in MYCN-Amplified Neuroblastoma [ Cancer Sci, 2025, 10.1111/cas.70043]	PubMed: 40052411
Nuclear accumulation of YTHDF1 regulates mRNA splicing in the DNA damage response [ Sci Adv, 2025, 11(16):eado7660]	PubMed: 40238889
Oncogenic p53 induces mitotic errors in lung cancer cells by recopying DNA replication forks conferring targetable proliferation advantage [ Res Sq, 2025, rs.3.rs-7303237]	PubMed: 40831504
Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma [ Nat Biomed Eng, 2024, 10.1038/s41551-024-01273-9]	PubMed: 39658630
Inhibition of topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats [ Nat Commun, 2024, 15(1):5727]	PubMed: 38977669
ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I [ Cell Death Dis, 2024, 15(7):519]	PubMed: 39033176

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。

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