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LY2606368

现货
Catalog No.
B1088
CHK1抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 2,200.00
Ship with 10-15 days
25mg
¥ 6,600.00
Ship with 10-15 days

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Background

LY2606368 is a selective ATP competitive inhibitor of checkpoint kinase 1(CHK1) with IC50 value of 1.5nM in SW1990 cells [1].

CHK1 is an intracellular serine/threonine kinase that plays a role in DNA damage response pathway. The inhibitors of CHK1 are developed for the treatment of cancers. LY2606368 is an ATP-competitive inhibitor of CHK1 and is undergoing clinical trials currently. It inhibits the auto-phosphorylation of CHK1 and induces the phosphorylation of H2AX in cancer cells. In the pancreatic cell line SW1990, LY2606368 significantly inhibits cell proliferation with IC50 value of 1.5nM. LY2606368 also exerts potent anti-tumor activity in SW1990 xenograft model. Besides that, in the orthotopic SKVO3 model, treatment of LY2606368 is found to inhibit tumor growth and reduce the incidence of metastases and accumulation. However, LY2606368 is only administered intravenously due to its poor oral bioavailability [1, 2 and 3].

References:
[1] Wu W, Bi C, Bence A K, et al. Antitumor activity of Chk1 inhibitor LY2606368 as a single agent in SW1990 human pancreas orthotopic tumor model. Cancer Research, 2012, 72(8 Supplement): 1776.
[2] Lainchbury M, Matthews T P, McHardy T, et al. Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino) pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. Journal of medicinal chemistry, 2012, 55(22): 10229-10240.
[3] McNeely S C, Burke T F, DurlandBusbice S, et al. Abstract A108: LY2606368, a second generation Chk1 inhibitor, inhibits growth of ovarian carcinoma xenografts either as monotherapy or in combination with standard-of-care agents. Molecular Cancer Therapeutics, 2011, 10(Supplement 1): A108.

Chemical Properties

StorageStore at -20°C
M.Wt365.39
Cas No.1234015-52-1
FormulaC18H19N7O2
Solubility<0.73mg/mL in DMSO
Chemical Name5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile
SDFDownload SDF
Canonical SMILESNCCCOC1=CC=CC(OC)=C1C2=CC(NC(C=N3)=NC=C3C#N)=NN2
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

Hela细胞

制备方法

溶解度有限,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

7 h

实验结果

LY2606368触发S期DNA损伤,如pH2AX(S139)和TUNEL阳性染色细胞在S期细胞中显著增加。LY2606368也需要CDC25A和CDK2来触发DNA损伤。此外,LY2606368导致复制灾变。

动物实验: [1]

动物模型

携带Calu-6肿瘤的雌性CD-1nu-/nu小鼠(26-28 g)

给药剂量

1、3.3或10 mg/kg,每天两次,持续3天

实验结果

在所测试的三个剂量LY2606368组中观察到高达72.3%的肿瘤生长抑制,小鼠的体重下降不超过3%,表明LY2606368在任何治疗组中耐受性良好。此外,在28天恢复期间,最高剂量组的肿瘤再生长缓慢,表明肿瘤对LY2606368产生持久应答。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. King C, Diaz HB, McNeely S et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-13.

质量控制

化学结构

LY2606368