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SCH900776

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Chemical Structure| 891494-63-6 同义名 : MK-8776
CAS号 : 891494-63-6
货号 : A200833
分子式 : C15H18BrN7
纯度 : 99%+
分子量 : 376.254
MDL号 : MFCD20922873
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(279.07 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • CDK2

    CDK2, IC50:0.16 μM

  • Chk1

    Chk1, IC50:3 nM
描述 Chk1 (Checkpoint kinase 1), an important serine/threonine kinase, is responding to DNA damage and stall DNA replication. Chk1 plays a key role in maintaining the replication fork viability during exposure to DNA antimetabolites. Inhibition of Chk1 will lead to accumulation of double-strand DNA breaks and cell death in human tumor cell lines exposure to anti-metabolite. SCH 900776 (MK-8776) is a selective and highly potent CHK1 inhibitor with IC50 value of 3 nM (measured by kinase assays), modest to CDK2 and Chk2 with much higher IC50 values of 160 nM and 1.5 μM, respectively. Treatment with 8 - 500 nM of SCH 900776 for 2h led to dose-dependent accumulation of DNA double-strand breaks induced by hydroxyurea in U2OS cells (measured by g-H2AX, a biomarker of DNA double-strand breaks). Consistent with that, 0.06 – 2 μM SCH 900776 for 2h caused decreased level of p-Ser296 site of Chk1 (an autophosphorylation site of Chk1) in U2OS cells exposure to hydroxyurea. SCH 900776 can induce a dose-dependent loss of DNA replication capability (measured by BrdU positive cells number) after the hydroxyurea exposure. An increase in the sub-G1 population was also observed, suggesting the cell death within the culture. Consistent with that, SCH 900776 exposure can enhance apoptosis for at least 48h following release from hydroxyurea blockade. Intraperitoneally injection of 8 - 32 mg/kg SCH-900776, 30 minutes after gemcitabine (150 mg/kg) 3 cycles of treatment on every fifth day, can lead to enhanced tumor pharmacodynamic and regression responses relative to either agent alone in the A2780 xenografted models[1]. Up to now, a phase I study of SCH-900776 in combination with gemcitabine in solid tumours and lymphoma has been completed[2].
作用机制 SCH-900776 is an ATP competitive inhibitor[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A2058 37.5-300 nM Cell Viability Assay 72 h reduces the MK-1775 EC50 by 5-fold to an average of 45 nM 23148684
A498 200/2000 nM Growth Inhibition Assay 24 h decreases the IC50 of Gemcitabine 24359526
AsPC-1 200/2000 nM Growth Inhibition Assay 24 h decreases the IC50 of Gemcitabine 24359526
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.29mL

2.66mL

1.33mL

26.58mL

5.32mL

2.66mL
参考文献

[1]Guzi TJ, Paruch K, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.

[2]Matthews TP, Jones AM, et al. Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anticancer therapies. Expert Opin Drug Discov. 2013 Jun;8(6):621-40.