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INCB28060

现货
Catalog No.
A8448
C-Met抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 660.00
现货
10mg
¥ 980.00
现货
50mg
¥ 3,150.00
Ship with 10-15 days
100mg
¥ 5,250.00
Ship with 10-15 days

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Background

INCB28060, also known as Capmatinib and INC280, is a novel and ATP-competitive inhibitor of c-Met with IC50 of 0.13 nM.

c-Met, also named as hepatocyte growth factor receptor (HGFR) is a receptor tyrosine kinase that is essential for embryonic development and would healing. In many tumor cells, this molecular is overexpressed or mutated and was found to play important roles in tumor cell proliferation, survival, invasion, metastasis and angiogenesis.

In vitro, INCB28060 treatment effectively inhibited activation of c-MET and signaling in cancer cells. As a result, INCB28060 blocked cell proliferation of varying cell lines such as SNU-5 and S114. The cell migration of U-87MG and H441 cells were also highly inhibited1.

The role of c-met was studied using this inhibitor in mouse model. Oral administration of INCB28060 leads to inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models. Therefore, INCB28060 has the therapeutic potential in cancer treatment 1.

Reference:
1.   Liu X, Wang Q, Yang G, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011;17(22):7127-7138.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt412.42
Cas No.1029712-80-8
FormulaC23H17FN6O
Solubility≥5.15mg/mL in DMSO with gentle warming
Chemical Name2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide
SDFDownload SDF
Canonical SMILESCNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
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]:

激酶实验

测定缓冲液含有50 mM Tris-HCl、10 mM MgCl2,100 mM NaCl,0.1mg/ml BSA、5mM DTT、pH 7.8。对于HTS,将0.8μL 5 mM溶解在DMSO中的测试化合物点在384孔板上。为了测量IC50,通过3倍和11点连续稀释制备化合物板。将0.8 μL的DMSO中的化合物从化合物板转移到测定板。在测定缓冲液中制备8 nM未磷酸化的c-Met或0.5 nM磷酸化c-Met的溶液。将溶解在DMSO中的1 mM的肽底物生物素EQEDEPEGDYFEWLE酰胺的1 mM储备液在含有400 μM ATP(未磷酸化c-Met)或160 μM ATP(磷酸化c-Met)的测定缓冲液中稀释至1 μM。将20 μL体积的酶溶液加入每个板中的适当孔中,然后每孔加入20 μL的底物溶液以引发反应。保护板免受光照,并在25℃温育90分钟。通过加入20 μL含有45 mM EDTA、50 mM Tris-HCl、50mM NaCl、0.4 mg/ml BSA、200 nM SA-APC和3 nM EU-Py20的溶液来终止反应。将板在室温下孵育15-30分钟,并在Perkin Elmer Fusionα-FP仪器上测量HTRF(均匀时间分辨荧光)。

动物实验 [2]:

细胞系

人肿瘤细胞系(SNU-5、SNU-1、U-87MG、786-O、A549、H441、H596、H1437、H1993、BT474、A549和HT-29), MKN-45细胞系,S114细胞系,来自于健康人群和癌症患者的血液样本

溶解方法

在DMSO中的溶解度有限。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

IC50: 0.13 nM (c-MET),72小时

应用

在SNU-5人胃癌细胞系中,INCB28060(IC50:1nM)抑制人c-MET磷酸化和c-MET介导的信号转导。INCB28060抑制SNU-5的活力或增殖,平均IC50值为1.2 nM。INCB28060(2 nM)阻止HGF刺激的H441细胞迁移。在c-MET依赖性肿瘤模型中,INCB28060表现出很强的抗肿瘤活性。INCB28060显示皮摩尔浓度的酶效力,对c-MET具有高度特异性,跟人类其它激酶相比具有超过10,000倍的选择性。INCB28060(24小时)有效抑制c-MET依赖性肿瘤细胞增殖和迁移,有效诱导细胞凋亡。

动物实验 [2]:

动物模型

皮下注射S114肿瘤细胞或U-87MG胶质母细胞瘤肿瘤细胞雌性Balb/c nu/nu小鼠(Charles River)

给药剂量

0.03、0.1、0.3、1、3或10 mg/kg

应用

在c-MET驱动的小鼠肿瘤模型中,口服给药INCB28060以时间和剂量依赖性方式抑制c-MET磷酸化和肿瘤生长。在实现完全肿瘤抑制的剂量下,INCB28060具有良好的耐受性。在10只U-87MG荷瘤小鼠中,每日给药10 mg/kg INCB28060导致6只小鼠的肿瘤部分消退。

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]. Behshad E, Klabe R M, Margulis A, et al. Phosphorylation state-dependent high throughput screening of the c-MET kinase[J]. Current chemical genomics, 2010, 4: 27.

[2]. Liu X, Wang Q, Yang G, et al. A novel kinase inhibitor INCB28060 blocks c-MET-dependent signaling, neoplastic activities, and crosstalk with EGFR and HER-3[J]. Clinical Cancer Research, 2011: clincanres. 1157.2011.

生物活性

Description INCB28060是新型的ATP竞争性C-MET抑制剂,其IC50值为0.13 nM。
靶点 c-MET          
IC50 0.13 nM          

质量控制

质量控制和MSDS

批次:

化学结构

INCB28060