Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors

Anna Vulpetti, Elena Casale, Fulvia Roletto, Raffaella Amici, Manuela Villa, Paolo Pevarello

Research output: Contribution to journalArticlepeer-review

Abstract

N-(5-Bromo-1,3-thiazol-2-yl)butanamide (compound 1) was found active (IC50 = 808 nM) in a high throughput screening (HTS) for CDK2 inhibitors. By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3- thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50 = 20 nM). The syntheses, structure-based analog design, kinases inhibition data and X-ray crystallographic structures of CDK2/inhibitor complexes are reported.

Original languageEnglish
Pages (from-to)341-348
Number of pages8
JournalJournal of Molecular Graphics and Modelling
Volume24
Issue number5
DOIs
Publication statusPublished - Mar 2006

Keywords

  • CDK2
  • Crystal structures
  • Cyclin-dependent kinase
  • Ligand docking
  • Ligand-protein interactions
  • Structure-based drug design

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Spectroscopy
  • Atomic and Molecular Physics, and Optics

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