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 journal › Article

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

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inhibitors
drugs
Pharmaceutical Preparations
Screening
Phosphotransferases
Crystal structure
Throughput
X rays
screening
analogs
crystal structure
2-aminothiazole
synthesis
x rays
benzenesulfonamide

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

Cite this

Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors. / Vulpetti, Anna; Casale, Elena; Roletto, Fulvia; Amici, Raffaella; Villa, Manuela; Pevarello, Paolo.

In: Journal of Molecular Graphics and Modelling, Vol. 24, No. 5, 03.2006, p. 341-348.

Research output: Contribution to journal › Article

Vulpetti, A, Casale, E, Roletto, F, Amici, R, Villa, M & Pevarello, P 2006, 'Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors', Journal of Molecular Graphics and Modelling, vol. 24, no. 5, pp. 341-348. https://doi.org/10.1016/j.jmgm.2005.09.012
Vulpetti A, Casale E, Roletto F, Amici R, Villa M, Pevarello P. Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors. Journal of Molecular Graphics and Modelling. 2006 Mar;24(5):341-348. https://doi.org/10.1016/j.jmgm.2005.09.012
Vulpetti, Anna ; Casale, Elena ; Roletto, Fulvia ; Amici, Raffaella ; Villa, Manuela ; Pevarello, Paolo. / Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors. In: Journal of Molecular Graphics and Modelling. 2006 ; Vol. 24, No. 5. pp. 341-348.
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