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• 产品描述： PHA-767491 is a potent ATP-competitive dual Cdc7/CDK9 inhibitor with IC50 of 10 nM and 34 nM, respectively.

• 靶点： CDK;cholecystokinin;GSK-3;cholecystokinin;GSK-3;CDK

• 体外研究：
  PHA-767491降低Chk1磷酸化并增加从裸鼠HCC异种移植物切片的肿瘤组织中的原位细胞凋亡

• 体内研究：
  PHA-767491抑制两种细胞系的增殖,在HCC1954细胞中的IC50为0.64 μM,在Colo-205细胞中的IC50为1.3 μM。PHA-767491（2 μM）在HCC1954细胞中24小时完全消除Mcm2磷酸化。PHA-767491与5-FU联用对HCC细胞表现出更强的细胞毒性并诱导显著的凋亡,表现为显著增加的胱天蛋白酶3激活和聚（ADP-核糖）聚合酶片段化。 PHA-767491直接抵消5-FU诱导的Chk1的磷酸化并降低抗凋亡蛋白髓性白血病细胞1ine的表达。 PHA-767491（0-10 μM）以时间和剂量依赖方式降低成胶质细胞瘤细胞活力,U87-MG和U251-MG细胞的IC50约为2.5 μM

• 细胞实验： For assays in 96 well plates 2500 cells are plated per well. After 24 hours, cells are treated with small molecule inhibitors and incubated for 72 hours at 37°C. Subsequently the cells are lysed and the ATP content is measured as an indicator of metabolically active cells using the CellTiter-Glo assay. IC50 values are calculated using the GraphPad software. For assays in six well plates, 100,000 cells are plated per well. After 24 hours, cells are treated with small molecule inhibitors and incubated for varying time points. Cells are trypsinized and a suspension is made in 5 mL of phosphate buffered saline. 30 μL of this suspension is mixed with 30 μL of CellTiter-Glo reagent followed by a 10-minute incubation at room temperature. Luminescence is measured using EnVision 2104 Multilabel Reader and BioTek Synergy Neo Microplate Reader.

• 参考文献：
  1. Yecies D, et al. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood, 2010, 115(16), 3304-3313. 2. Natoni A, et al. Mechanisms of action of a dual Cdc7/Cdk9 kinase inhibitor against quiescent and proliferating CLL cells. Mol Cancer Ther, 2011, 10(9), 1624-1634. 3. Montagnoli A, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol, 2008, 4(6), 357-365.

• 溶解性： soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	4.69 ml	23.448 ml	46.896 ml
  5 mM	0.938 ml	4.69 ml	9.379 ml
  10 mM	0.469 ml	2.345 ml	4.69 ml
  50 mM	0.094 ml	0.469 ml	0.938 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *