Pharmacophore identification, docking and ''in silico'' screening for novel CDK1 inhibitors

X. Dong, J. Yan, Lin Du, Peng Wu, S. Huang, T. Liu, Y. Hu

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Pharmacophore models of cyclin-dependent kinase-1 (CDK1) inhibitors were established by using the Catalyst/HypoGen. The best pharmacophore model, Hypo1, consists of one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), one hydrophobic (HY) and one ring aromatic (RA) feature. The
validation results of Hypo1 through cost analysis, test set prediction, Fisher’s cross method and receiver operating characteristic (ROC) study indicated that the Hypo1 was statistically valuable and reliable in identifying structural diverse CDK1 inhibitors. It is further supported by the consistent results from molecular
docking studies. Finally, the Hypo1 was used to “in silico” screen the NCI and MayBridge database. The preferable hits obtained were further docked into ATP binding site of CDK1, and nine promising compounds were retrieved as novel potential CDK1 inhibitors for further studies.
Original languageEnglish
JournalJournal of Molecular Graphics and Modelling
Volume37
Pages (from-to)77-86
ISSN1093-3263
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • CDK1 inhibitors
  • Pharmacophore
  • HypoGen
  • Homology modeling
  • LigandFit

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