title: Setting up a kinase discovery and development project.
abstract: Discovery of novel kinase inhibitors has matured rapidly over the last decade. Paramount to the successful development of kinase inhibitors is appropriate selectivity for validated targets. Many different approaches have been applied over the years, with varied results. There are currently thirteen different small molecule protein kinase inhibitors on the marketplace. Interestingly, a majority of these compounds lack precise selectivity for specific targets. This will change in the coming years, as technology for achieving improved selectivity becomes more widely applied. This chapter will focus on some of the critical considerations in setting up a kinase discovery and development project, citing examples particularly targeting the Raf kinases.
authors.affiliation: Plexxikon Inc, Berkeley, CA 94710, USA. gbollag@plexxikon.com
authors.forename: Gideon
authors.initials: G
authors.lastname: Bollag
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D004789:Enzyme Activation; D057075:Enzyme Assays / Q000379:methods; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D000077157:Sorafenib; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D048490:raf Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D007211:Indoles; C528407:PLX 4720; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D009536:Niacinamide; D000255:Adenosine Triphosphate; D000077157:Sorafenib; D048490:raf Kinases