BioDrugs

, Volume 18, Issue 3, pp 167–180 | Cite as

Kinase Targets and Inhibitors for the Treatment of Airway Inflammatory Diseases

The Next Generation of Drugs for Severe Asthma and COPD?
Novel Therapeutic Strategies

Abstract

Kinases are believed to play a crucial role in the expression and activation of inflammatory mediators in the airway, in T-cell function, and in airway remodeling. Important pro-inflammatory transcription factors such as activating protein-1 and nuclear factor κB, which are activated in airway disease, require kinase activation to switch on inflammatory genes, while other kinases can regulate mRNA half-life. Selective kinase inhibitors have been developed that reduce inflammatory gene expression and some characteristics of disease in animal models. Targeting specific kinases that are overexpressed or overactive in disease should allow for selective treatment of airway inflammatory diseases. Interest in this area has intensified due to the success of the specific Abelson murine leukemia viral oncogene homolog tyrosine kinase inhibitor, imatinib mesylate, in the treatment of chronic myelogenous leukemia. Encouraging data from animal models and primary cells and early phase I and II studies in other diseases suggest that inhibitors of p38 mitogen-activated protein kinase and inhibitor of κB kinase-2 may prove to be useful novel therapies in the treatment of severe asthma and chronic obstructive pulmonary disease.

Notes

Acknowledgements

The authors would like to acknowledge funding from The Wellcome Trust, National Institutes of Health, the British Lung Foundation, Associazone per la ricerca e la cura dell Asma, AstraZeneca, GlaxoSmithKline, Mitsubishi and Pfizer. We regret that due to space limitations we were not able to cite all the important original work and apologize to those authors whose work we have not cited.

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Thoracic Medicine, National Heart and Lung InstituteImperial College LondonLondonUK

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