| 产品描述： | AZ20 is an effective and specific inhibitor of ATR kinase (IC50: 5 nM, in a cell-free assay), 8-fold selectivity over mTOR |
| 靶点： |
mTOR;ATM/ATR;ATM/ATR; mTOR |
| 体外研究： |
AZ20（10 μM）可使CYP3A4介导的咪达唑仑代谢的50％被抑制.LoVo肿瘤的雌性裸鼠中,服用13天AZ20（25 mg/kg,2次/天,p.o.;50 mg/kg/day,p.o. ）可使肿瘤生长受到显著抑制,这与异种移植组织中γH2AX核染色的持续广泛升高有关 |
| 体内研究： |
在体外,AZ20浓度依赖性地降低pChk1 Ser345/317/296水平。延长AZ20的处理时间可增加γH2AX核染色,这是因为存在复制压力,且与S期阻滞和组蛋白H3的磷酸化水平增加有关。AZ20对体外生长抑制和细胞死亡的诱导作用是完全不同于其它细胞毒性药物的。AZ2与ATM 抑制剂KU-60019联用会增加细胞毒性 |
| 细胞实验： |
AZ20 is dissolved in 100% DMSO. Compound dose ranges are created by diluting in 100% DMSO and then further into assay medium (EMEM, 10% FCS, 1% glutamine) using a Labcyte Echo acoustic dispensing instrument. Cells are plated in 384-well Costar plates at 9×104 cells per mL in 40 μL of EMEM, 10% FCS, 1% glutamine and grown for 24 h. Following addition of compound the cells are incubated for 60 min. A final concentration of 3 μM 4NQO (prepared in 100% DMSO) is then added using the Labcyte Echo, and the cells are incubated for a further 60 min. The cells are fixed by adding 40 μL of 3.7% v/v formaldehyde solution for 20 min. After removal of fix, cells are washed with PBS and permeabilized in 40 μL of PBS containing 0.1% Triton X-100. The cells are then washed, and 15 μL primary antibody solution (pChk1 Ser345) is added. The plates are incubated at 4°C overnight. The primary antibody is then washed off, and 20 μL of secondary antibody solution and 1 μM Hoechst 33258 added for 90 min at room temperature. The plate |
| 参考文献： |
1. Foote KM, et al. Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J Med Chem, 2013, 56(5), 2125-2138. |
| 溶解性： |
Soluble in DMSO、Ethanol |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.424 ml |
12.121 ml |
24.242 ml |
| 5 mM |
0.485 ml |
2.424 ml |
4.848 ml |
| 10 mM |
0.242 ml |
1.212 ml |
2.424 ml |
| 50 mM |
0.048 ml |
0.242 ml |
0.485 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京