title: What is the potential for inhaled p38 inhibitors in the treatment of chronic obstructive pulmonary disease?
abstract: p38 has been an intensely studied therapeutic target in the pharmaceutical industry. With more than 20 compounds entering human trials, none have progressed beyond Phase II to the best of our knowledge. The transient efficacy seen in many of the Phase II trials has raised some concerns for the future potential of this target, particularly in rheumatoid arthritis. With this caveat, there is good evidence for p38 inhibition to be efficacious in chronic obstructive pulmonary disease and there are now several oral compounds currently in development for this disease, with encouraging data beginning to emerge. With an inhaled agent likely to improve the therapeutic window between efficacy and some of the common adverse events observed with oral p38 inhibitors it would seem a sensible approach to take for a disease of the lung. This review will highlight the potential for an inhaled p38 inhibitor in chronic obstructive pulmonary disease, as well as some of the design principles that are important to consider when developing an inhaled kinase inhibitor.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Kent, CT13 9NJ, UK. dave.millan@gmail.com
authors.forename: David S
authors.initials: DS
authors.lastname: Millan
mesh_terms: D000280:Administration, Inhalation; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases