title: Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases.
abstract: BACKGROUND
  In asthma and chronic obstructive pulmonary disease (COPD), airway mucus hypersecretion contributes to impaired mucociliary clearance, mucostasis and, potentially, the development of mucus plugging of the airways.
  
  
  CONCLUSIONS
  Excess mucus production can be targeted via therapies that focus on inhibition mucin synthesis, via reducing expression of mucin (MUC) genes, and/or inhibition of mucin secretion into the airways.
  
  
  CONCLUSIONS
  This review discusses a number of therapeutic approaches to reduce airway mucus in asthma and COPD, including the use of synthetic and natural products. In particular, it highlights areas where clinical trials of inhibitors of particular target molecules are lacking. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are an example of a targeted therapy that has been researched to reduce mucus synthesis, as have inhibitors of EGFR's downstream signalling pathways, for example, mitogen-activated protein kinase-13 and hypoxia inducible factor-1. However, their efficacy and safety profiles are currently not up to the mark. There is clinical potential in Bio-11006, which reduces mucus secretion via the inhibition of myristoylated alanine-rich C-kinase substrate and is currently in Phase IIb trial.
authors.affiliation: National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Emily V S
authors.initials: EV
authors.lastname: Ha
authors.forename: Duncan F
authors.initials: DF
authors.lastname: Rogers
mesh_terms: D056151:Airway Remodeling / Q000502:physiology; D001249:Asthma / Q000503:physiopathology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004610:Ellagic Acid / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D018756:GABA Antagonists; D046934:Ginkgolides / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors; D018836:Inflammation Mediators / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D048292:Mitogen-Activated Protein Kinase 13 / Q000037:antagonists & inhibitors; D009077:Mucins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism*; D051938:Munc18 Proteins / Q000037:antagonists & inhibitors; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D058470:Receptors, Purinergic P2Y
chemical_list: C492109:CLCA1 protein, human; D018118:Chloride Channels; D018756:GABA Antagonists; D046934:Ginkgolides; D018840:HSP70 Heat-Shock Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051793:Hypoxia-Inducible Factor 1; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; D007783:Lactones; D018942:Macrolides; D008565:Membrane Proteins; D009077:Mucins; D051938:Munc18 Proteins; D058470:Receptors, Purinergic P2Y; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D004610:Ellagic Acid; C045856:ginkgolide B; D048292:Mitogen-Activated Protein Kinase 13; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases