Journal of Computer-Aided Molecular Design

, Volume 32, Issue 9, pp 901–915 | Cite as

Discovery of novel wee1 inhibitors via structure-based virtual screening and biological evaluation

  • Yaping Li
  • Yinglan Pu
  • Hui Liu
  • Li Zhang
  • Xingyong Liu
  • Yan LiEmail author
  • Zhili ZuoEmail author


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 µM and a Ki value of 13.11 µM. 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 µM. 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.


Wee1 inhibitors Pharmacophore model Molecular docking Virtual screening Molecular dynamics simulation 



This work was financially supported by CAS “Light of West China” Program ([2014]91 to Z.Z.), CAS Strategic biological resources service network (ZSTH-021), the Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDA12030206.

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Supplementary material

10822_2018_122_MOESM1_ESM.docx (3.2 mb)
Supplementary material 1 (DOCX 3321 KB)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of BotanyChinese Academy of SciencesKunmingChina
  2. 2.School of Chemical EngineeringSichuan University of Science & EngineeringZigongChina

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