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MK-8776 (SCH-900776)

现货
Catalog No.
A8477
Chk1高效选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,210.00
现货
5mg
¥ 1,100.00
现货
10mg
¥ 1,600.00
现货
50mg
¥ 4,500.00
现货

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Background

SCH 900776 is a potent and selective inhibitor of cell cycle checkpoint kinase 1 (Chk1), Chk2 and Cdk3 with IC50 value of 3 nM, 1.5µM and 0.16 µM, respectively.

Chk is s serine/threonine kinase that senses signal of DNA damage and stalls DNA replication, and also plays an essential role in the maintenance of replication fork viability during exposure to DNA antimetabolites.

In vitro, SCH 900776 blocked accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Treatment of proliferating WS1 cells with SCH 900776 was found to be associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 in response to the inhibition of SCH 900776 as part of a futile cycle 1.

In BALB/c mice, administration of SCH 900776 at a dosage of 8mg/kg after gemcitabine treatment can sufficiently induce enhanced tumor pharmacodynamic and regression responses as compared to gemcitabine or SCH 900776 alone 1.

Reference:
1.   Guzi TJ, Paruch K, Dwyer MP, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high
content screening. Molecular cancer therapeutics. 2011;10(4):591-602.

文献引用

1. Bourgeois A, Bonnet S, et al. "Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension." Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1667-1681. PMID:31092016

Chemical Properties

StorageStore at -20°C
M.Wt376.25
Cas No.891494-63-6
FormulaC15H18BrN7
Solubility≥18.8mg/mL in DMSO, <1.91 mg/mL in EtOH, <1.88 mg/mL in H2O
Chemical Name(R)-6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine
SDFDownload SDF
Canonical SMILESBrC(C([C@@H]1CCCNC1)=N2)=C(N)N3C2=C(C4=CN(C)N=C4)C=N3
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

U2OS细胞

溶解方法

该化合物在DMSO中的溶解度大于18.8 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

2h

应用

在U2OS细胞中,在羟基脲暴露24小时后,SCH 900776以剂量依赖性方式损伤DNA复制能力。从羟基脲封闭释放后,SCH 900776增加细胞凋亡至少48小时。

动物实验 [1]:

动物模型

A2780异种移植的BALB/c小鼠

给药剂量

4-32 mg/kg

应用

SCH-900776(8 mg/kg)增强肿瘤药效学和回归反应。SCH 900776(16和32 mg/kg)诱导肿瘤反应的增加。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1] Guzi T J, Paruch K, Dwyer M P, et al. Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening[J]. Molecular cancer therapeutics, 2011, 10(4): 591-602.

生物活性

Description SCH-900776是Chk1的选择性抑制剂,其IC50值为3 nM。
靶点 Chk1 CDK2 Chk2      
IC50 3 nM 0.16 μM 1.5 μM      

质量控制

化学结构

MK-8776(SCH-900776)

相关生物数据

MK-8776(SCH-900776)