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VE-822

现货
Catalog No.
B1383
ATR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 990.00
现货
10mg
¥ 1,030.00
现货
50mg
¥ 3,290.00
现货

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Background

VE-822 is an ATR inhibitor with an IC50 value of 0.019 μM. It is a close analog of VE-821 with a marked increase in potency against ATR.
Radiation (XRT) and chemotherapy induce chromosomal DNA lesions resulting in activation of the ataxia telangiectasiamutated (ATM) and ATM-Rad3-related (ATR) protein kinases in response to double-strand DNA breaks (DSBs) and replication stress, respectively. Defects in the DNA damage response (DDR) such as ATM and p53 deletion/mutation are common in human tumors and occur in up to 70% of patients with PDAC. They might lead to a differential response in DNA repair signaling between normal and tumor cells that could be exploited to increase killing of Radiation (XRT) and chemotherapy induce chromosomal DNA lesions.
In irradiated cancer cells, VE-822 decreased checkpoints of cell-cycle, decreased homologous recombination and increased persistent DNA damage. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity.
Reference:
1.Fokas E, Prevo R, Pollard JR et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441.

文献引用

1. Koppenhafer SL, Goss KL, et al. "mTORC1/2 and protein translation regulate levels of CHK1 and the sensitivity to CHK1 inhibitors in Ewing sarcoma cells." Mol Cancer Ther. 2018 Oct 3. pii: molcanther.0260.2018. PMID:28808226
2. Le TM, Poddar S, Capri JR, et al. "ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways." Nat Commun. 2017 Aug 14;8(1):241. PMID:28808226

Chemical Properties

StorageStore at -20°C
M.Wt463.55
Cas No.1232416-25-9
FormulaC24H25N5O3S
Solubility≥50mg/mL in DMSO
Chemical Name3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine
SDFDownload SDF
Canonical SMILESCC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)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

细胞实验: [1]

细胞系

胰腺导管腺癌细胞(PDAC)

制备方法

溶解度有限,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

1-2 h

实验结果

VE-822降低辐射p53突变体和K-Ras突变体PDAC的存活。在化学放射治疗后,VE-822和gemcitabine的组合给药减少存活2-3倍。此外,VE-822增加辐射诱导的残余gH2AX和53BP1病灶,并减少辐射后Rad51病灶。

动物实验: [1]

动物模型

胰腺癌异种移植物雌性Balb/c裸鼠

给药剂量

口服,60 mg/kg

制备方法

10%维生素E d-α生育酚聚乙二醇1000琥珀酸酯

实验结果

在给予DNA损伤剂后,VE-822抑制磷酸-Ser-345-Chk1。与单独的辐射相比,VE-822和辐射的组合显著延长了肿瘤生长延迟。此外,与gemcitabine+辐射的组合相比,VE-822+gemcitabine+辐射的组合组中的肿瘤生长延迟时间更长。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Fokas E, Prevo R, Pollard JR et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441.

质量控制

化学结构

VE-822

相关生物数据

VE-822

相关生物数据

VE-822