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AZD7762

现货
Catalog No.
A5919
ATP竞争性的检查点激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
现货
5mg
¥ 700.00
现货
25mg
¥ 2,400.00
现货
100mg
¥ 4,700.00
现货

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Background

AZD7762 is a novel ATP competitive inhibitor of checkpoint kinases. Chk family checkpoint kinases include Chk1 and Chk2. They are activated in response to DNA damage and phosphorylate CDC25A, CDC25C protein phosphatases, which delay cell cycle progression. Therefore, Chk activation initiates cell cycle checkpoint, causes cell cycle arrest, and allows DNA repair.

AZD7762 is a potent selective inhibitor of Chk1. It binds to the ATP binding pocket and compete ATP binding in a reversible manner. AZD7762 inhibits Chk1 phosphorylation of CDC25C peptide with an IC50 of 5 nM. The Ki is 3.6 nM. It is equally potent against Chk2 but less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. [1]

AZD7762 prevents cell cycle arrest and DNA repair in DNA damaged tumor cells, causing tumor cell apoptosis. Hence, it potentiates the antitumor activity of DNA damaging agents and can be used as a chemosensitizing agent. [2]

Half life of AZD7762 is 1-2 hours in mice [3]

References:
[1]Zabludoff SD, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther, 2008, 7(9): 2955-2966.
[2]Landau HJ, et al. The checkpoint kinase inhibitor AZD7762 potentiates chemotherapy-induced apoptosis of p53-mutated multiple myeloma cells. Mol Cancer Ther. 2012, 11(8): 1781-1788
[3]Goteti K, et al. Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Cancer Chemother Pharmacol. 2010, 66(2): 245-254.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt362.42
Cas No.860352-01-8
FormulaC17H19FN4O2S
Solubility≥18.1mg/mL in DMSO, <2.89 mg/mL in EtOH, <2.37 mg/mL in H2O
Chemical Name3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide
SDFDownload SDF
Canonical SMILESC1CC(CNC1)NC(=O)C2=C(C=C(S2)C3=CC(=CC=C3)F)NC(=O)N
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

T47D和 MCF7细胞

制备方法

该化合物在DMSO中的溶解度大于10 mM,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

100 nM,24 hours

实验结果

在p53突变的T47D细胞中,AZD7762显著增强辐射敏化作用,但在野生型p53 MCF7细胞中没有观察到相似的效果。在p53突变体T47D细胞中,AZD7762与放射组合使用产生的细胞毒性显著大于单独放射引起的细胞毒性。在野生型p53 MCF7细胞中,AZD7762使细胞产生对辐射敏感的趋势,但该差异未达到统计学显著性。

动物实验: [2]

动物模型

注射HT-29细胞的雌性无胸腺裸鼠

给药剂量

腹腔注射,25 mg/kg,在放射治疗后立即给予和8小时后给予

实验结果

AZD7762单独治疗对肿瘤生长几乎没有影响,而分次给药延迟肿瘤生长。单独使用AZD7762、分次使用以及AZD7762分次使用结合辐射三组实验中,肿瘤达到初始测量的肿瘤体积三倍的时间为2.3(P < 0.53),7.4(P < 0.07)和18.7(P < 0.00014) 天。相对于单独的分次辐射,AZD7762和分次辐射的组合具有显著性效果。因此,与单独处理相比,AZD7762和分次辐射的组合使用更大程度延迟肿瘤生长。

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] Ma Z, Yao G, Zhou B, et al. The Chk1 inhibitor AZD7762 sensitises p53 mutant breast cancer cells to radiation in vitro and in vivo. Molecular medicine reports, 2012, 6(4): 897-903.

[2] Mitchell J B, Choudhuri R, Fabre K, et al. In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clinical Cancer Research, 2010, 16(7): 2076-2084.

生物活性

描述 AZD7762是一种有效的和选择性的Chk1抑制剂,IC50值为5 nM。
靶点 CHK1 CHK2        
IC50 5 nM <10 nM        

质量控制

化学结构

AZD7762

相关生物数据

AZD7762

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AZD7762

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AZD7762