中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1

文献类型:期刊论文

作者Yi, Ping1,2; Qiu, Minghua1
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2008-03-01
卷号43期号:3页码:604-613
关键词3d-qsar Gold Comfa C-jun N-terminal Kinase-1
ISSN号0223-5234
DOI10.1016/j.ejmech.2007.04.020
文献子类Article
英文摘要In order to better understand the structural and chemical features of c-Jun N-terminal kinase-1 (JNK-1), which is a member of the mitogen activated protein kinase (MAP kinase) family of enzymes responsible for the serine/threonine phosphorylation of intracellular targets, 3D-QSAR studies of some aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors were performed by comparative molecular field analysis (CoMFA) to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The genetic algorithm of GOLD3.1 has been employed to position 54 aminopyridine carboxamides in the active sites of JNK-1 to determine the probable binding conformation. The docking results provided a reliable conformational alignment scheme for 3D-QSAR model. Based on the docking conformations, highly predictive comparative molecular field analysis (CoMFA) was performed with a cross-validated q(2) of 0.585. The non-cross-validated analysis with six optimum components revealed a conventional r(2) value of 0.988, F = 5 10.200, and an estimated standard error of 0.071. Furthermore, the CoMFA model was mapped back to the binding sites of JNK-1, to get a better understanding of vital interactions between the aminopyridine carboxamides and the kinase. Based on the docking and CoMFA analyses, we have identified some key features in the aminopyridine carboxamides that are responsible for JNK-1 inhibitory activity. The analyses may be used to design more potent aminopyridine carboxamides and predict their activity prior to synthesis. (c) 2007 Elsevier Masson SAS. All rights reserved.
学科主题Chemistry ; Medicinal
WOS关键词INSULIN-RECEPTOR SUBSTRATE-1 ; BINDING-AFFINITY ; FLEXIBLE DOCKING ; PHOSPHORYLATION ; VALIDATION ; RESISTANCE ; PATHWAYS ; SER(307) ; JNK
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000254777400017
公开日期2011-11-24
源URL[http://ir.kib.ac.cn:8080/handle/151853/1897]  
专题昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Yunnan, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China
推荐引用方式
GB/T 7714
Yi, Ping,Qiu, Minghua. 3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2008,43(3):604-613.
APA Yi, Ping,&Qiu, Minghua.(2008).3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,43(3),604-613.
MLA Yi, Ping,et al."3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 43.3(2008):604-613.

入库方式: OAI收割

来源:昆明植物研究所

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