Kinases as targets: prospects for chronic therapy.
Several inhibitors of protein kinases have been launched or have reached late stages of clinical trials for the treatment of acute conditions such as cancer. Development was slow, mainly because of the associated toxicity, attributed to the poor selectivity of these compounds. Protein kinase inhibitors mainly bind at the active site of the enzyme, in competition with ATP, and whether such inhibitors could ever be used for the long-term treatment of chronic conditions, such as rheumatoid arthritis, is still questionable. This review concentrates on three enzymes, well established as potential drug targets for the treatment of chronic inflammatory conditions, and considers progress made in developing potent and selective inhibitors that could progress through clinical trials and eventually be launched on the market.
Orchard
Sandra
S
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. orchard@ebi.ac.uk
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002908:Chronic Disease / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases