Discovery of novel indoleaminopyrimidine NIK inhibitors based on molecular docking-based support vector regression (SVR) model

doi:10.1016/j.cplett.2019.01.031

	Discovery of novel indoleaminopyrimidine NIK inhibitors based on molecular docking-based support vector regression (SVR) model
	Ye, Qing 3; Li, Qiu 2,3; Gao, Anhui 1; Ying, Huazhou 2; Cheng, Gang 4; Chen, Jing 4; Che, Jinxin 2; Li, Jia 1; Dong, Xiaowu 2; Zhou, Yubo 1
刊名	CHEMICAL PHYSICS LETTERS
	2019-03-01
卷号	718 页码:38-45
ISSN号	0009-2614
DOI	10.1016/j.cplett.2019.01.031
通讯作者	Dong, Xiaowu(dongxw@zju.edu.cn) ; Zhou, Yubo(ybzhou@simm.ac.cn)
英文摘要	A set of NF-kappa B-inducing kinase (NIK) inhibitors was used to develop a molecular docking-based QSAR model by using nonlinear regression method. The accuracy of the QSAR model was remarkably improved by integrating the docking scores and key interaction profiles. Two indole-aminopyrimidine derivatives 32a and 32b predicted as NIK inhibitors were synthesized and biologically evaluated. The significant correlationship between experimental data and MD-SVR model-predicted results were observed. The binding mode of 32a and 32b with NIK were further investigated by dynamic simulations. Compound 32b was proposed as a promising lead for the findings of highly potent inhibitors.
资助项目	Postdoctoral Science Foundation of China[2014M550256] ; Postdoctoral Science Foundation of China[2017M612017] ; State Key Laboratory of Drug Research[SIMM1403KF-02] ; State Key Laboratory of Drug Research[SIMM1705KF-08] ; Natural Science Foundation of China[81502926] ; Science and Technology Planning Project of Zhejiang Province[2014C37050] ; National Science & Technology Major ProjectKey New Drug Creation and Manufacturing Program, China[2018ZX09711002-007]
WOS关键词	ACTIVATION ; DESIGN ; DESCRIPTORS ; COMBINATION ; PRINCIPLES ; LIGANDFIT ; PATHWAY
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000458812300007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290528]
专题	中国科学院上海药物研究所
通讯作者	Dong, Xiaowu; Zhou, Yubo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China 3.Zhejiang Univ Technol, State Key Lab Breeding Base Green Chem Synth Tech, Hangzhou 310032, Zhejiang, Peoples R China 4.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 311402, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Ye, Qing,Li, Qiu,Gao, Anhui,et al. Discovery of novel indoleaminopyrimidine NIK inhibitors based on molecular docking-based support vector regression (SVR) model[J]. CHEMICAL PHYSICS LETTERS,2019,718:38-45.
APA	Ye, Qing.,Li, Qiu.,Gao, Anhui.,Ying, Huazhou.,Cheng, Gang.,...&Zhou, Yubo.(2019).Discovery of novel indoleaminopyrimidine NIK inhibitors based on molecular docking-based support vector regression (SVR) model.CHEMICAL PHYSICS LETTERS,718,38-45.
MLA	Ye, Qing,et al."Discovery of novel indoleaminopyrimidine NIK inhibitors based on molecular docking-based support vector regression (SVR) model".CHEMICAL PHYSICS LETTERS 718(2019):38-45.