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 language | English |
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Pages (from-to) | 341-348 |
Number of pages | 8 |
Journal | Journal of Molecular Graphics and Modelling |
Volume | 24 |
Issue number | 5 |
DOIs | |
Publication status | Published - 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