Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway
文献类型：期刊论文
| 作者 | Liang, Zhongjie1,2; Ai, Jing1 ; Ding, Xiao1; Peng, Xia1; Zhang, Dengyou1; Zhang, Ruihan1; Wang, Ying1; Liu, Fang1; Zheng, Mingyue1; Jiang, Hualiang1
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| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2013-04 |
| 卷号 | 4期号:4页码:408-413 |
| 关键词 | Anthraquinone derivatives c-Met kinase inhibitors binding affinity with HGF |
| ISSN号 | 1948-5875 |
| DOI | 10.1021/ml4000047 |
| 文献子类 | Article |
| 英文摘要 | The aberrant function of c-Met kinase signaling pathway is ubiquitously involved in a broad spectrum of human cancers; thus, a strong rationale exists for targeting the kinase pathway in cancer therapy. Via integration of computational and experimental studies, anthraquinone derivatives were identified for the first time as potent c-Met kinase inhibitors in this research. The aberrant activation of the c-Met kinase pathway results from (TPR)-Met, MET gene mutation, or amplification and a hepatocyte growth factor (HGF)/scatter factor-dependent autocrine or paracrine mechanism. However, anthraquinone derivatives exclusively suppressed c-Met phosphorylation stimulated by HGF in A549 cells, indicating that the compounds possess the ability to block the extracellular HGF-dependent pathway. A surface plasmon resonance assay revealed that the most potent compound, 2a, shows a high binding affinity for HGF with an equilibrium dissociation constant of 1.95 mu M. The dual roles of compound 2a demonstrate the potency of anthraquinone derivatives and provide a new design solution for the c-Met kinase signaling pathway. |
| WOS关键词 | PHARMACOPHORE MODEL ; DISCOVERY ; CANCER ; DESIGN |
| 资助项目 | 863 program[2012AA020302] ; State Key Program of Basic Research of China[2009CB918502] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09507-004] ; National Natural Science Foundation of China[81025017] ; National Natural Science Foundation of China[30725046] ; National Natural Science Foundation of China[81102461] ; National Natural Science Foundation of China[81021062] ; National Natural Science Foundation of China[91029704] ; National Natural Science Foundation of China[21210003] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000317553300008 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277670]  |
| 专题 | 药物化学研究室 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 药物发现与设计中心 药理学第一研究室 |
| 通讯作者 | Liu, Hong |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Soochow Univ, Ctr Syst Biol, Suzhou 215006, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Liang, Zhongjie,Ai, Jing,Ding, Xiao,et al. Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway[J]. ACS MEDICINAL CHEMISTRY LETTERS,2013,4(4):408-413. |
| APA | Liang, Zhongjie.,Ai, Jing.,Ding, Xiao.,Peng, Xia.,Zhang, Dengyou.,...&Luo, Cheng.(2013).Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway.ACS MEDICINAL CHEMISTRY LETTERS,4(4),408-413. |
| MLA | Liang, Zhongjie,et al."Anthraquinone Derivatives as Potent Inhibitors of c-Met Kinase and the Extracellular Signaling Pathway".ACS MEDICINAL CHEMISTRY LETTERS 4.4(2013):408-413. |
入库方式： OAI收割
来源：上海药物研究所
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