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AMG-900

现货
Catalog No.
A4119
Aurora激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,200.00
现货
5mg
¥ 1,100.00
现货
10mg
¥ 1,900.00
现货
50mg
¥ 5,900.00
现货
200mg
¥ 14,900.00
现货

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Background

AMG900 is a highly sensitive and orally bioavailable inhibitor of Aurora Kinase with IC50 values of 5 nmol/L.

AMG900 is an inhibitor of all three aurora kinase family members. It was founded through the discovery of a new class of ATP-competitive phtha-lazinamine small molecule inhibitors of aurora kinases. AMG900 inhibits autophosphorylation of aurora-A and aurora-B in tumor cells, and also aborts cell division without a prolonged mitosis arrest and finally results cell death. It can inhibit 26 different tumor cell lines proliferation, meanwhile, it also has the ability to enhance other aurora kinase inhibitors' effective. [1, 2]

AMG900 had been tested in animal level using mice models. Mice bearing established HCT116 tumors and orally delivery AMG900. Comparing to the vehicle group, the experiment groups delivery AMG900 with different concentration showed an obvious smaller tumor volume. These results revealed that AMG900 has the ability to significantly inhibit tumor growth.

References:
1.  Payton, M., et al., Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res, 2010. 70(23): p. 9846-54.
2.  Geuns-Meyer, S., et al., Discovery of N-(4-(3-(2-Aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4- (4-methylthiophen-2-yl)p hthalazin-1-amine (AMG 900), A Highly Selective, Orally Bioavailable Inhibitor of Aurora Kinases with Activity against Multidrug-Resistant Cancer Cell Lines. J Med Chem, 2015. 58(13): p. 5189-207.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt503.58
Cas No.945595-80-2
FormulaC28H21N7OS
Solubility≥25.2 mg/mL in DMSO, <2.3 mg/mL in EtOH, <2.21 mg/mL in H2O
Chemical NameN-[4-[3-(2-aminopyrimidin-4-yl)pyridin-2-yl]oxyphenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine
SDFDownload SDF
Canonical SMILESCC1=CSC(=C1)C2=NN=C(C3=CC=CC=C32)NC4=CC=C(C=C4)OC5=C(C=CC=N5)C6=NC(=NC=C6)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

激酶实验 [1]:

激酶试验

使用杆状病毒系统表达GST或His标记的aurora-A (TPX2) 和aurora-B重组蛋白,采用亲和色谱法进行纯化。使用标准的均相时间分辨荧光 (HTRF) 法评估AMG 900活性。以相似的方法测定其它24种酶 (aurora-C、p38α、TYK2、JNK2、JAK3、c-Met、VEGFR2、p38β、TIE-2、ABL (T315I)、ERK1、BTK、JNK3、CDK5、PKAα、JNK1、p70S6K、PKBα、MSK1、LCK、SRC、IGFR、JAK2、和c-KIT)。根据激酶特异性和相应底物Km值优化反应中的酶、多肽底物以及ATP浓度。在蛋白激酶组竞争结合试验(n = 353种特定激酶)中通过Ambit Biosciences评估AMG 900活性。以1000 nM的单一浓度初步筛选AMG 900。对于每个结合位点(少于对照组的20%),测定其定量结合常数(Kd)。

细胞实验 [1]:

细胞系

人结肠癌HCT116细胞系

制备方法

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 °C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 °C可放置数月。

反应条件

50 nM;48小时

实验结果

AMG 900诱导具有裂解活性的caspase-7,从而呈时间依赖性地增加细胞凋亡。

动物实验 [1]:

动物模型

携带HCT116肿瘤的裸鼠

给药剂量

3.75、7.5或15 mg/kg;口服给药;3、6或9小时

实验结果

AMG 900呈剂量依赖性地显著抑制HCT116肿瘤。

其它注意事项

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]. Payton, M., et al., Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res, 2010. 70(23): p. 9846-54.

生物活性

Description AMG-900是一种有效的和高选择性的Aurora激酶抑制剂,对Aurora A、B和C的IC50值分别为5 nM、4 nM和1 nM。
靶点 Aurora A Aurora B Aurora C      
IC50 5 Nm 4 nM 1 nM      

质量控制

化学结构

AMG-900