Discovery of novel wee1 inhibitors via structure-based virtual screening and biological evaluation
Li, Yaping1,2; Pu, Yinglan2; Liu, Hui2; Zhang, Li2; Liu, Xingyong2; Li, Yan1; Zuo, Zhili1,2
2018-09-01
发表期刊JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
ISSN0920-654X
卷号32期号:9页码:901-915
摘要Wee1 plays a critical role in the arrest of G2/M cell cycle for DNA repair before entering mitosis. Many cancer cells have been identified as overexpression of Wee1. In this research, pharmacophore modeling, molecular docking and molecular dynamics simulation approaches were constructed to identify novel potential Wee1 inhibitors. A compound 8 was found to have a novel skeleton against Wee1 with an IC50 value of 22.32 mu M and a K-i value of 13.11 mu M. Kinetic assays were employed to evaluate the compound 8 as a competitive inhibitor. Compound 8 was tested against A-549 tumor cell lines with IC50 value of 17.8 mu M. To investigate the intermolecular interaction of Wee1 and compound 8, further molecular dynamics simulations were performed. It indicates that the binding mode of compound 8 and reference ligand is similar. The active core scaffold of compound 8 could represent a promising lead compound for studying Wee1 and be used for further structural optimization to design more potent Wee1 inhibitors.
关键词Wee1 inhibitors Pharmacophore model Molecular docking Virtual screening Molecular dynamics simulation
资助信息CAS "Light of West China" Program; CAS Strategic biological resources service network; Strategic Priority Research Program of the Chinese Academy of Sciences
语种英语
资助项目CAS "Light of West China" Program[[2014]91] ; CAS Strategic biological resources service network[ZSTH-021] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12030206]
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/62551
专题植物化学与西部植物资源持续利用国家重点实验室
通讯作者Li, Yan; Zuo, Zhili
作者单位1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
2.Sichuan Univ Sci & Engn, Sch Chem Engn, Zigong 643000, Sichuan, Peoples R China
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GB/T 7714
Li, Yaping,Pu, Yinglan,Liu, Hui,et al. Discovery of novel wee1 inhibitors via structure-based virtual screening and biological evaluation[J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,2018,32(9):901-915.
APA Li, Yaping.,Pu, Yinglan.,Liu, Hui.,Zhang, Li.,Liu, Xingyong.,...&Zuo, Zhili.(2018).Discovery of novel wee1 inhibitors via structure-based virtual screening and biological evaluation.JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN,32(9),901-915.
MLA Li, Yaping,et al."Discovery of novel wee1 inhibitors via structure-based virtual screening and biological evaluation".JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN 32.9(2018):901-915.
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