Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors

doi:10.1016/j.ejmech.2017.11.073

	Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors
	Yuan, Haoliang 1,2; Liu, Qiufeng3,4,5 ; Zhang, Li 1; Hu, Shihe 1; Chen, Tiantian 3; Li, Huifang 6; Chen, Yadong 1; Xu, Yechun 3; Lu, Tao 1,2
	2018-01
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (IF:6.0[JCR-2023],6.1[5-Year])
ISSN	0223-5234
卷号	143 页码:491-502
发表状态	已发表
DOI	10.1016/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
引用统计	正在获取...
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
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.