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SGX-523

现货
Catalog No.
A1196
高度选择性的、ATP竞争性的Met抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 870.00
Ship with 10-15 days
5mg
¥ 1,160.00
Ship with 10-15 days
25mg
¥ 3,360.00
Ship with 10-15 days
100mg
¥ 7,800.00
Ship with 10-15 days

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Background

SGX-523 is a novel, potent, ATP-competitive, and highly-selective Hepatocyte growth factor receptor (MET) inhibitor with IC50 value of 4 nM [1].

SGX523 inhibits MET autophosphorylation in gastric cancer cell line GTL16 and human lung carcinoma cell line A549, with IC50 of 40 nM and 12 nM, respectively [1]. Additionally, tumor regression was observed in gastic cancer cell line GTL16 and human GBM cell line U87MG derived mouse xenograft models that are treated with SGX-523 by oral gavage [1].

SGX523 has been shown to inhibit the phosphorylateion of MEK, MAPK, AKT in brain cancer cell lines including U87, U373, DAOY, as well as glioma stem cells 1228. The inhibition of MEK in brain cancer cells and stem cells led to cell proliferation, G1/S cell cycle progression, cell migration, and cell invasion [2].

References:
[1] Buchanan SG1, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF,Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K,Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90.
[2] Guessous F1, Zhang Y, diPierro C, Marcinkiewicz L, Sarkaria J, Schiff D, Buchanan S, Abounader R.An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anticancer Agents Med Chem. 2010 Jan;10(1):28-35.

文献引用

1. Shi P, Oh YT, et al. "Met gene amplification and protein hyperactivation is a mechanism of resistance to both first and third generation EGFR inhibitors in lung cancer treatment." Cancer Lett. 2016 Jul 19;380(2):494-504. PMID:27450722

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt359.41
Cas No.1022150-57-7
FormulaC18H13N7S
Solubility≥17.95mg/mL in DMSO
Chemical Name6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl]quinoline
SDFDownload SDF
Canonical SMILESCN1C=C(C=N1)C2=NN3C(=NN=C3SC4=CC5=C(C=C4)N=CC=C5)C=C2
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

加入100 mM HEPES (pH 7.5),0.3 mg/mL聚谷氨酸-酪氨酸多肽底物,10 mM MgCl2,1 mg/mL牛血清蛋白,5% DMSO,20 nM MET-KD以及各种浓度的ATP和SGX523,在21 °C下,测定初始速率。加入20 μL Kinase-Glo测定缓冲液终止反应。使用光度计测定荧光,通过回归曲线分析结果。

细胞实验 [1]:

细胞系

MDCK细胞

制备方法

在DMSO中的溶解度大于18 mg/mL。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

0.04、0.12、0.36和3.0 μM;过夜

实验结果

在犬肾上皮MDCK细胞中,SGX-523阻止HGF诱导的细胞分散。

动物实验 [1]:

动物模型

携带GTL16胃癌细胞异种移植物的裸鼠

给药剂量

10、20、30、100 mg/kg,每日2次,或60 mg/kg,每日1次;口服给药

实验结果

在剂量大于10 mg/kg(每日2次)的情况下,SGX523显著抑制GTL16异种移植物生长。此外,SGX523显著抑制MET激酶活性。

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]. Buchanan SG1, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF,Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K,Wasserman SR, Emtage S, Burley SK, Reich SH. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90.

生物活性

描述 SGX-523是高度选择性的Met抑制剂,IC50值为4 nM。
靶点 Met          
IC50 4 nM          

质量控制

化学结构

SGX-523

相关生物数据

SGX-523

相关生物数据

SGX-523

相关生物数据

SGX-523