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VE-821

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Catalog No.
A2521
ATR激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 900.00
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5mg
¥ 700.00
现货
25mg
¥ 2,000.00
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100mg
¥ 6,800.00
现货

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Background

VE-821 is a potent, highly-selective, and ATP-competitive DNA damage response (DDR) kinase ATR inhibitor with Ki value of 13nM. VE-821 specifically inhibits ATR, revealing low cross-reactivity against the mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), phosphoinositol 3-kinase-γ (PI3K) and the related PIKKs ATM [1].

HL-60 cells treated with VE-821 (10μM) showed reduction of phosphorylatin of Chk1 (Ser 345), inhibition of cell growth, and a radiosensitizing effect after Gamma-ray irradiation [2].

VE-821 has also been demonstrated to down-regulate the phosphorylated Chk1 (Ser 345) but it does not inhibit the phosphorylation of Chk2 (Thr68) and ATM (Ser1981) in pancreatic cancer cell lines, including PSN-1 and MiaPaCa-2 cells that are treated with gemcitabine or radiation. VE-821 combined with gemcitabine (a nucleoside analog) has caused a remarkable increase of cytotoxic effect of gemcitabine against hypoxia [3].

References:
[1] Reaper PM1, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011 Apr 13;7(7):428-30.
[2] Vávrová J1, Zárybnická L, Lukášová E, Řezáčová M, Novotná E, Sinkorová Z, Tichý A, Pejchal J, Durišová K. Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60). Radiat Environ Biophys. 2013 Nov;52(4):471-9.
[3] Prevo R1, Fokas E, Reaper PM, Charlton PA, Pollard JR, McKenna WG, Muschel RJ, Brunner TB.The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012 Sep;13(11):1072-81.

文献引用

1. Li Z, Liu B, et al. "hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability." EMBO J. 2018 May 17. pii: e96729. PMID:29773570
2. Nanda Kumar Sasi, Flavie Coquel, et al. "DDK has a primary role in processing stalled replication forks to initiate downstream checkpoint signaling." bioRxiv. 2017.October 21.

Chemical Properties

StorageStore at -20°C
M.Wt368.41
Cas No.1232410-49-9
FormulaC18H16N4O3S
Solubility≥62.5mg/mL in DMSO
Chemical Name2-(aminomethyl)-6-[4,6-diamino-3-[4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol;sulfuric acid
SDFDownload SDF
Canonical SMILESCS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

抑制活性

使用Millipore KinaseProfiler服务研究VE-821(2μM)对指定的人(h)、大鼠(r)、小鼠(m)和裂殖酵母(y)激酶的活性,ATP浓度等于每种酶ATP的Km值。

细胞实验[1]:

细胞系

HFL1细胞, HCT116肿瘤细胞,H23癌细胞系

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

10 μM,24、48或96 小时

实验结果

在加入200 μM顺铂(Cis)、1 μM吉西他滨(Gem)、100μM依托泊苷(Etop)或5Gy电离辐射(IR)之前,使用10 μM VE-821或DMSO预处理HFL1细胞,在所有条件下,VE-821阻断Chk1Ser345 磷酸化,并且在用cisplatin和gemcitabine治疗中抑制H2AX磷酸化。在H23癌细胞系中,VE-821与cisplatin协同作用,在生长停滞中发挥显著作用。

References:

[1]. Reaper PM1, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat ChemBiol, 2011, 7(7): 428-430.

生物活性

描述 VE-821是一种有效的、选择性的和ATP竞争性的ATR激酶抑制剂,Ki/IC50值分别为13 nM/26 nM。
靶点 ATR          
IC50 13 nM/26 nM (Ki/IC50)          

质量控制

化学结构

VE-821

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