The role of structure in kinase-targeted inhibitor design
Pratt, D.J.; Endicott, J.A.; Noble, M.E.M.
Current Opinion in Drug Discovery and Development 7(4): 428-436
2004
ISSN/ISBN: 1367-6733 PMID: 15338952 Document Number: 579159
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.