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Chemical Structure| 1232416-25-9 同义名 : VE-822;VX970;M6620
CAS号 : 1232416-25-9
货号 : A172242
分子式 : C24H25N5O3S
纯度 : 99%+
分子量 : 463.552
MDL号 : MFCD27976794
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • ATR

    ATR, IC50:19 nM
描述 ATR/ATM kinases can phosphorylate a broad and overlapping catalogue of several thousand substrates in DNA damage signaling. The kinase activity of ATR, activated by single-stranded DNA (ssDNA) coated with replication protein A (RPA), is increased at damaged replication forks and resected DNA double-strand breaks (DSBs). VE-822 is a close analog of VE-821, possessing a marked potency against ATR with Ki value < 0.2nM, as well as cell IC50 value of 19nM. The cell study showed that VE-822 can attenuate ATR signaling pathway and reduce survival in tumor cells in response to XRT and gemcitabine. Treatment with VE-822 (80nM) reduced pChk1-Ser345, as the major marker for ATR inhibition, after gemcitabine (100 nM), XRT (6 Gy) or both in MiaPaCa-2 and PSN-1 cells or in vivo study, alone with dramatically reduced survival of these two tumor cells (but not in normal cells). 1h pre-treatment with 80nM VE-822 increased XRT-induced residual γH2AX and 53BP1 foci, whereas no effect on VE-822 alone, suggesting the enhancement of residual DNA damage by VE-822 in vitro. Oral administration with VE-822 at dose of 60mg/kg enhanced the therapeutic efficacy of radiation (XRT) in MiaPaCa-2 and PSN-1 xenograft models, as well as enhanced tumor response in combination with XRT and gemcitabine in PSN-1 xenografts[1].
作用机制 VE-822 is a close analog of VE-821, which acts as an ATP-competitive inhibitor of ATR.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HCK1T-HPV16 0.5 nM Function Assay 24 h  increases the levels of E1 25717108
HCK1T-HPV16 0.5 nM Function Assay 24 h  enhances E1-dependent replication of the HPV16 genome 25717108
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.79mL

2.16mL

1.08mL

21.57mL

4.31mL

2.16mL
参考文献

[1]Fokas E, Prevo R, 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.

[2]Josse R, Martin SE, et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.