Kinases as Novel Therapeutic Targets in Asthma and Chronic Obstructive Pulmonary Disease. 2016

Peter J Barnes
National Heart and Lung Institute, Imperial College, London, United Kingdom p.j.barnes@imperial.ac.uk.

Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD. However, it has proven difficult to develop selective kinase inhibitors that are both effective and safe after oral administration and this has led to a search for inhaled kinase inhibitors, which would reduce systemic exposure. Although many kinases have been implicated in inflammation and remodeling of airway disease, very few classes of drug have reached the stage of clinical studies in these diseases. The most promising drugs are p38 MAP kinases, isoenzyme-selective PI3-kinases, Janus-activated kinases, and Syk-kinases, and inhaled formulations of these drugs are now in development. There has also been interest in developing inhibitors that block more than one kinase, because these drugs may be more effective and with less risk of losing efficacy with time. No kinase inhibitors are yet on the market for the treatment of airway diseases, but as kinase inhibitors are improved from other therapeutic areas there is hope that these drugs may eventually prove useful in treating refractory asthma and COPD.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000893 Anti-Inflammatory Agents Substances that reduce or suppress INFLAMMATION. Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein
D058990 Molecular Targeted Therapy Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease. Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular
D029424 Pulmonary Disease, Chronic Obstructive A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA. Airflow Obstruction, Chronic,COAD,COPD,Chronic Airflow Obstruction,Chronic Obstructive Airway Disease,Chronic Obstructive Lung Disease,Chronic Obstructive Pulmonary Disease,Chronic Obstructive Pulmonary Diseases,Airflow Obstructions, Chronic,Chronic Airflow Obstructions

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