title: The role of structure in kinase-targeted inhibitor design.
abstract: Protein kinases are attractive targets for rational drug design against a wide range of diseases. From detailed knowledge of the structure-function relationships underlying protein kinase activity and regulation, a number of methods for achieving kinase inhibition have been suggested and explored using structure-aided drug discovery. Attaining selective protein kinase inhibition in a cellular context, and converting the large number of known potent kinase inhibitors into effective drugs, are outstanding problems in this area and, from a structural perspective, the challenges presented by modulating pharmacokinetics and minimizing the incidence of resistant mutations in the target are of particular interest.
authors.affiliation: Oxford University, Laboratory of Molecular Biophysics, The Rex Richards Building, South Parks Road, Oxford, OX1 3QU, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pratt
authors.forename: Jane A
authors.initials: JA
authors.lastname: Endicott
authors.forename: Martin E M
authors.initials: ME
authors.lastname: Noble
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011494:Protein Kinases