Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors
2018-01
发表期刊EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (IF:6.0[JCR-2023],6.1[5-Year])
ISSN0223-5234
卷号143页码:491-502
发表状态已发表
DOI10.1016/j.ejmech.2017.11.073
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.
关键词c-Met Virtual screening Pharmacophore X-ray crystallography Structural optimization
收录类别SCI ; SCIE ; IC
语种英语
资助项目"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
WOS类目Chemistry, Medicinal
WOS记录号WOS:000428216700040
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS关键词CANCER ; EXPRESSION ; MUTATIONS ; RECEPTOR ; PROGRESS
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/20212
专题生命科学与技术学院
生命科学与技术学院_博士生
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.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
3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Key Lab Receptor Res, Shanghai 201203, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Univ British Columbia, Vancouver Prostate Ctr, 2660 Oak St, Vancouver, BC V6H 3Z6, Canada
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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.
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