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
Source PublicationJOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
ISSN0920-654X
Volume32Issue:9Pages:901-915
AbstractWee1 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.
KeywordWee1 inhibitors Pharmacophore model Molecular docking Virtual screening Molecular dynamics simulation
DOI10.1007/s10822-018-0122-1
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics ; Computer Science
WOS SubjectBiochemistry & Molecular Biology ; Biophysics ; Computer Science, Interdisciplinary Applications
WOS IDWOS:000445757800003
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/62551
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorLi, Yan; Zuo, Zhili
Affiliation1.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
Recommended Citation
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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