The role of structure in kinase-targeted inhibitor design.
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.
Pratt
David J
DJ
Oxford University, Laboratory of Molecular Biophysics, The Rex Richards Building, South Parks Road, Oxford, OX1 3QU, UK.
Endicott
Jane A
JA
Noble
Martin E M
ME
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
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases