Simm530, a novel and highly selective c-Met inhibitor, blocks c-Met-stimulated signaling and neoplastic activities
文献类型：期刊论文
| 作者 | Wang, Ying2; Zhan, Zhengsheng3; Jiang, Xifei1,4; Peng, Xia2; Shen, Yanyan2; Chen, Fang3; Ji, Yinchun2; Liu, Weiren1,4; Shi, Yinghong1,4; Duan, Wenhu3
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| 刊名 | ONCOTARGET
 |
| 出版日期 | 2016-06-21 |
| 卷号 | 7期号:25页码:38091-38104 |
| 关键词 | c-Met kinase inhibitor Simm530 |
| ISSN号 | 1949-2553 |
| DOI | 10.18632/oncotarget.9349 |
| 文献子类 | Article |
| 英文摘要 | The aberrant c-Met activation has been implicated in a variety of human cancers for its critical role in tumor growth, metastasis and tumor angiogenesis. Thus, c-Met axis presents as an attractive therapeutic target. Notably, most of these c-Met inhibitors currently being evaluated in clinical trials lack selectivity and target multiple kinases, often accounting for the undesirable toxicities. Here we described Simm530 as a potent and selective c-Met inhibitor. Simm530 demonstrated >2,000 fold selectivity for c-Met compared with other 282 kinases, making it one of the most selective c-Met inhibitors described to date. This inhibitor significantly blocked c-Met signaling pathways regardless of mechanistic complexity implicated in c-Met activation. As a result, Simm530 led to substantial inhibition of c-Met-promoted cell proliferation, migration, invasion, ECM degradation, cell scattering and invasive growth. In addition, Simm530 inhibited primary human umbilical vascular endothelial cell (HUVEC) proliferation, decreased intratumoral CD31 expression and plasma pro-angiogenic factor interleukin-8 secretion, suggesting its significant anti-angiogenic properties. Simm530 resulted in dose-dependent inhibition of c-Met phosphorylation and tumor growth in c-Met-driven lung and gastric cancer xenografts. And, the inhibitor is well tolerated even at doses that achieve complete tumor regression. Together, Simm530 is a potent and highly selective c-Met kinase inhibitor that may have promising therapeutic potential in c-Met-driven cancer treatment. |
| WOS关键词 | HEPATOCYTE GROWTH-FACTOR ; SMALL-MOLECULE INHIBITOR ; SCATTER-FACTOR ; KINASE INHIBITOR ; TYROSINE KINASE ; ACQUIRED-RESISTANCE ; ONCOGENE ADDICTION ; INVASIVE GROWTH ; GASTRIC-CANCER ; RECEPTOR |
| 资助项目 | National Program on Key Basic Research Project of China[2012CB910704] ; National Key Sci-Tech Project[2012ZX09301001-007] ; Natural Science Foundation of China[81321092] ; Natural Science Foundation of China[81473243] |
| WOS研究方向 | Oncology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000378229100054 |
| 出版者 | IMPACT JOURNALS LLC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275990]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Ai, Jing; Geng, Meiyu |
| 作者单位 | 1.Fudan Univ, Dept Liver Surg, Liver Canc Inst, Zhongshan Hosp, Shanghai 200433, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 200031, Peoples R China; 4.Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Ying,Zhan, Zhengsheng,Jiang, Xifei,et al. Simm530, a novel and highly selective c-Met inhibitor, blocks c-Met-stimulated signaling and neoplastic activities[J]. ONCOTARGET,2016,7(25):38091-38104. |
| APA | Wang, Ying.,Zhan, Zhengsheng.,Jiang, Xifei.,Peng, Xia.,Shen, Yanyan.,...&Geng, Meiyu.(2016).Simm530, a novel and highly selective c-Met inhibitor, blocks c-Met-stimulated signaling and neoplastic activities.ONCOTARGET,7(25),38091-38104. |
| MLA | Wang, Ying,et al."Simm530, a novel and highly selective c-Met inhibitor, blocks c-Met-stimulated signaling and neoplastic activities".ONCOTARGET 7.25(2016):38091-38104. |
入库方式： OAI收割
来源：上海药物研究所
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