A multitude of kinases--which are the best targets in treating rheumatoid arthritis?
Small-molecule kinase inhibitors are increasingly taking center stage in the quest for new drugs for the treatment of rheumatoid arthritis (RA). By targeting kinases, small-molecule inhibitors can exert potent anti-inflammatory and immunomodulatory effects; the success of small-molecule kinase inhibitors in the treatment of cancer has spurred efforts to identify kinases that could be targeted for the treatment of chronic inflammatory disorders, such as RA. Although many kinase inhibitors have proved efficacious in the treatment of inflammatory arthritis in animals few have been tested in RA clinical trials. This article discusses the challenges and progress in the pursuit of small-molecule kinase inhibitors for RA, including lessons learned from the failure of erstwhile frontrunner inhibitors and the promise of inhibitors making their debut on the RA stage.
Geriatric Research Education and Clinical Center (GRECC), MC154R, VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. tlind@stanford.edu <tlind@stanford.edu>
Tamsin M
TM
Lindstrom
William H
WH
Robinson
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases