The use of computational methods in the discovery and design of kinase inhibitors.
The recent success of the first FDA-approved small-molecule tyrosine kinase inhibitor Gleevec (STI-571, imatinib mesylate) in the treatment of chronic myelogenous leukemia (CML) has focused attention on the potential therapeutic usefulness of inhibitors of other kinase targets. This review shall highlight recent applications of computational chemistry methods, comprising both ligand-based and structure-based approaches, in the discovery and design of kinase inhibitors. In particular, we will focus on ATP-competitive inhibitors of selected kinase targets of therapeutic importance.
Woolfrey
John R
JR
Millennium Pharmaceuticals, Inc., South San Francisco, CA 94080, USA. john.woolfrey@mpi.com
Weston
G S
GS
D020650:Combinatorial Chemistry Techniques; D017076:Computer-Aided Design; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors; D021281:Quantitative Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008024:Ligands; D047428:Protein Kinase Inhibitors