Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors
文献类型：期刊论文
| 作者 | Yuan, Haoliang1,6; Liu, Qiufeng2,3,4; Zhang, Li1; Hu, Shihe1; Chen, Tiantian2; Li, Huifang5; Chen, Yadong1; Xu, Yechun2 ; Lu, Tao1,6
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2018 |
| 卷号 | 143页码:491-502 |
| 关键词 | c-Met Virtual screening Pharmacophore X-ray crystallography Structural optimization |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2017.11.073 |
| 文献子类 | Article |
| 英文摘要 | The c-Met kinase has emerged as an attractive target for developing antitumor agents because of its close relationship with the development of many human cancers, poor clinical outcomes and even drug resistance. A series of novel c-Met kinase inhibitors have been identified with multiple workflow in this work, including virtual screening, X-ray crystallography, biological evaluation and structural optimization. The experimentally determined crystal structure of the best hit compound HL-11 in c-Met kinase domain was highly consistent with the computational prediction. Comparison of the hit compounds with different c-Met kinase inhibitory activity by molecular dynamics simulations suggested the key protein-ligand interactions for structural optimization. Based on these, structural optimization produced compound 11e with better c-Met kinase inhibitory activity and improved anti-proliferative activity. These experimental findings proved the reliability and efficiency of our in silico methods. This strategy will facilitate further lead discovery and optimization for novel c-Met kinase inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | CANCER ; EXPRESSION ; MUTATIONS ; RECEPTOR ; PROGRESS |
| 资助项目 | National Science Foundation of China[81422047] ; National Science Foundation of China[81473078] ; National Science Foundation of China[81703367] ; scientific research funds for new teacher of China Pharmaceutical University[3014070086] ; Fundamental Research Funds for the Central Universities[2632017PY12] ; "111 Project" from the Ministry of Education of China, the State Administration of Foreign Expert Affairs of China[111-2-07] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000428216700040 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272322]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Xu, Yechun; Lu, Tao |
| 作者单位 | 1.China Pharmaceut Univ, Sch Sci, Lab Mol Design & Drug Discovery, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 5.Univ British Columbia, Vancouver Prostate Ctr, 2660 Oak St, Vancouver, BC V6H 3Z6, Canada 6.China Pharmaceut Univ, Inst Pharmaceut Res, Jiangsu Key Lab Drug Discovery Metab Dis, State Key Lab Nat Med, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yuan, Haoliang,Liu, Qiufeng,Zhang, Li,et al. Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,143:491-502. |
| APA | Yuan, Haoliang.,Liu, Qiufeng.,Zhang, Li.,Hu, Shihe.,Chen, Tiantian.,...&Lu, Tao.(2018).Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,143,491-502. |
| MLA | Yuan, Haoliang,et al."Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 143(2018):491-502. |
入库方式： OAI收割
来源：上海药物研究所
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