Kinase inhibitors as drugs for chronic inflammatory and immunological diseases: progress and challenges

Abstract

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.

Keywords::

• autoimmune disease
• BTK
• Bruton's tyrosine kinase
• common γ
• chain
• cytokines
• delayed-type hypersensitivity
• dry eye
• DTH
• inflammation
• IRAK-4
• JAK-3
• Janus kinase
• p38
• PKCθ
• psoriasis
• rheumatoid arthritis
• Rho kinase
• SCID
• severe combined immunodeficiency
• STAT
• signal transducers and activators of transcription
• TYK
• Tyrosine kinase γc
• XID
• X-linked immunodeficiency
• XLA
• X-linked agammaglobulinemia

Acknowledgements

The authors would like to express their sincere gratitude to Vera Swensen for the excellent administrative assistance that she has provided during the preparation of the manuscript.

Notes