title: Structural biology in drug design: selective protein kinase inhibitors.
abstract: Protein kinases have a fundamental role in signal transduction pathways, and aberrant kinase activity has been observed in many diseases. In recent years, kinase inhibition has become a major area for therapeutic intervention and a variety of kinase inhibitor pharmacophores has been described. This review illustrates some of the efforts and results in the field of structure-based design of protein kinase inhibitors. The methods and results discussed here illustrate the power of structure-based design in lead discovery, for example via virtual screening and in guiding the optimization of the pharmacological properties of these molecules.
authors.affiliation: Merck Research Laboratories, PO Box 2000, RY50 105, Rahway, NJ 07065, USA. giovanna_scapin@merck.com
authors.forename: Giovanna
authors.initials: G
authors.lastname: Scapin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D053616:Janus Kinase 3; D011493:Protein Kinase C / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018909:src Homology Domains
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D011493:Protein Kinase C