Kinase inhibitors as drugs for chronic inflammatory and immunological diseases: progress and challenges.
At the time of writing, there are seven marketed kinase inhibitor drugs. The first kinase inhibitor, imatinib mesilate (Gleevec, Novartis), came to market in 2001, an inhibitor of the breakpoint cluster region (BCR)/Abelson murine leukemia oncogene homolog (ABL) fusion, platelet-derived growth factor (PDGF) receptor, and c-kit kinases. The most recent kinase inhibitor to come to market, disatinib (Sprycel, Bristol-Myers Squibb), acts on c-SRC, ABL and Bruton's tyrosine kinase. To date, kinase inhibitor drugs are approved for oncology and demonstrate that it is possible to develop compounds with relative selectivity for the target kinase against the broader kinome. However, the use of kinase inhibitors in chronic inflammatory and immunologic diseases may require greater selectivity for the target kinase. This review addresses the opportunities and challenges of kinase inhibition as a therapeutic approach in chronic immune and inflammatory disease.
Rokosz
Laura L
LL
Pharmacopeia, Inc., PO Box 5350, Princeton, NJ 08543-5350, USA.
Beasley
James R
JR
Carroll
Carolyn Diianni
CD
Lin
Tsung
T
Zhao
Jiuqiao
J
Appell
Kenneth C
KC
Webb
Maria L
ML
D000818:Animals; D001549:Benzamides; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D007154:Immune System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000069439:Dasatinib