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LY2801653

现货
Catalog No.
A3573
MET抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,460.00
现货
5mg
¥ 1,260.00
现货
10mg
¥ 2,000.00
现货
50mg
¥ 6,120.00
现货
100mg
¥ 9,000.00
现货

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Background

LY2801653 is a potent and orally bioavailable inhibitor of c-MET kinase with IC50 value of 2 nM [1].

C-MET kinase is also known as hepacyte growth factor receptor (HGFR), which is a membrane-associated tyrosine kinase receptor. HGF is the only ligand for this receptor. The binding of HGF induces conformational changes of c-MET and thus activate tyrosine kinase activity, to process downstream signaling. C-MET signaling regulate various cellular functions including cell proliferation, survival and apoptosis, and abnormal activation of c-MET kinase may trigger tumor growth, angiogenesis and metastasis.

Biochemical study and crystallization study identified LY2801653 was a potent ATP-competitive inhibitor of c-MET kinase, where the inhibition was completed by suppression of c-MET kinase phosphorylation [1]. In vitro study showed that 0.01-10 μM LY2801653 was able to completely block HGF-induced DU-145 cell scattering regulated by c-MET kinase, which demonstrated the inhibition of c-MET kinase activity. When LY2801653 was screened with a panel of cell lines, it was found more potent anti-proliferative activity of LY2801653 in those cell lines with MET gene expression than without MET gene expression [2].

Mice bearing U-87MG xenograft were treated with low dose (1.3 mg/kg) and high dose (12 mg/kg) LY2801653 once daily for 28 days, and the tissues were characterized. It was found that low dose treatment resulted in a trend of reducing the area of c-MET kinase-associated apoptosis while the high dose treatment resulted in significant reduced apoptosis area. Additionally, high dose resulted in the suppression of c-MET kinase-associated angiogenesis, and vessels tend to be normalized [2].These observations demonstrated the LY2801653 was able to disrupt c-MET kinase downstream signaling via inhibiting the c-MET kinase activity.

Reference:
[1] Yan S B et al. , LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2012, 31: 833-844.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt552.53
Cas No.1206799-15-6
FormulaC30H22F2N6O3
SynonymsLY-2801653;LY 2801653
Solubility≥27.65 mg/mL in DMSO, ≥5.02 mg/mL in EtOH with ultrasonic and warming, <2.49 mg/mL in H2O
Chemical NameN-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-5-yl]oxyphenyl]-1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxamide
SDFDownload SDF
Canonical SMILESCC1=CC=C(C(=O)N1C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C=C5C(=C4)C=NN5C)C6=CNN=C6)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

细胞实验[1]:

细胞系

人非小细胞肺癌H441细胞系

溶解方法

在DMSO中的溶解度大于27.7 mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0.01-10 μM, 2 h

应用

在H441细胞中,LY2801653抑制MET的磷酸化及下游信号转导,导致MET通路的阻滞。LY2801653也可抑制H441细胞的增殖、生长、迁移和侵袭。

动物实验[2]:

动物模型

6周龄的雌性严重联合免疫缺陷(SUID)小鼠

剂量

口服给药,20 mg/kg

应用

LY2801653抑制肿瘤的生长,显著抑制细胞有丝分裂和血管生成。和对照组相比,LY2801653处理显著抑制SUID小鼠中A549-luc-C8肿瘤的生长,并且没有明显的体重改变。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Wu W, Bi C, Credille K M, et al. Inhibition of Tumor Growth and Metastasis in Non–Small Cell Lung Cancer by LY2801653, an Inhibitor of Several Oncokinases, Including MET[J]. Clinical Cancer Research, 2013, 19(20): 5699-5710.

[2]. Kawada I, Hasina R, Arif Q, et al. Dramatic Antitumor Effects of the Dual MET/RON Small-Molecule Inhibitor LY2801653 in Non–Small Cell Lung Cancer[J]. Cancer research, 2014, 74(3): 884-895.

生物活性

描述 LY2801653是一种有效的和口服可利用的c-MET激酶小分子抑制剂,Ki值为2 nM。
靶点 c-MET          
IC50 2 nM (Ki)          

质量控制

化学结构

LY2801653