discoveryofanewseriesofimidazo12apyridinecompoundsasselectivecmetinhibitors
文献类型：期刊论文
| 作者 | Liu Tongchao1; Peng Xia2; Ma Yuchi2; Ji Yinchun2; Chen Danqi2 ; Zheng Mingyue2; Zhao Dongmei1; Cheng Maosheng1; Geng Meiyu2; Shen Jingkang2
|
| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2016 |
| 卷号 | 000期号:005页码:698 |
| 关键词 | 吡啶类化合物 抑制剂 咪唑 信号转导通路 细胞检测 新系 MDCK细胞 癌症治疗 |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim： Aberrant c-Met activation plays a critical role in cancer formation, progression and dissemination, as well as in development of resistance to anticancer drugs. Therefore, c-Met has emerged as an attractive target for cancer therapy. The aim of this study was to develop new c-Met inhibitors and elaborate the structure-activity relationships of identified inhibitors. Methods： Based on the predicted binding modes of Compounds ,5 and 14 in docking studies, a new series of c-Met inhibitor-harboring 3-（（1H-pyrrolo3,2-cpyridin-1-yl）sulfonyl）imidazo1,2-apyridine scaffolds was discovered. Potent inhibitors were identified through extensive optimizations combined with enzymatic and cellular assays. A promising compound was further investigated in regard to its selectivity, its effects on c-Met signaling, cell proliferation and cell scattering in vitro. Results： The most potent Compound 31 inhibited c-Met kinase activity with an ICso value of 12.8 nmol/L, which was 〉78-fold higher than those of a panel of 16 different tyrosine kinases. Compound 31 （8, 40, 200 nmol/L） dose-dependently inhibited the phosphorylation of c-Met and its key downstream Akt and ERK signaling cascades in c-Met aberrant human EBC-1 cancer cells. In 12 human cancer cell lines harboring different background levels of c-Met expression/activation, Compound 31 potently inhibited c-Met- driven cell proliferation. Furthermore, Compound 31 dose-dependently impaired c-Met-mediated cell scattering of MDCK cells. Conclusion： This series of c-Met inhibitors is a promising lead for development of novel anticancer drugs. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/285477]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.沈阳药科大学 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Liu Tongchao,Peng Xia,Ma Yuchi,et al. discoveryofanewseriesofimidazo12apyridinecompoundsasselectivecmetinhibitors[J]. actapharmacologicasinica,2016,000(005):698. |
| APA | Liu Tongchao.,Peng Xia.,Ma Yuchi.,Ji Yinchun.,Chen Danqi.,...&Xiong Bing.(2016).discoveryofanewseriesofimidazo12apyridinecompoundsasselectivecmetinhibitors.actapharmacologicasinica,000(005),698. |
| MLA | Liu Tongchao,et al."discoveryofanewseriesofimidazo12apyridinecompoundsasselectivecmetinhibitors".actapharmacologicasinica 000.005(2016):698. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。