title: New and developing non-adrenoreceptor small molecule drugs for the treatment of asthma.
abstract: Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas covered: New and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA. Data was reviewed from studies published up until November 2016. Expert opinion: Tiotropium improves lung function and has a modest effect in reducing exacerbations when added to ICS alone or ICS and LABA. The LAMAs umeclidinium and glycopyrronium are under development in fixed dose combination with ICS and LABA. Novel small molecule drugs, such as CRTH2 receptor antagonists, PDE4inhibitors, protein kinase inhibitors and nonsteroidal glucocorticoid receptor agonists and 'off-label' use of licensed drugs, such as macrolides and statins are under investigation for asthma, although their effectiveness in clinical practice is not established. To better achieve the goal of developing effective novel small molecule drugs for asthma will require greater understanding of mechanisms of disease and the different phenotypes and endotypes of asthma.
authors.affiliation: a Institute of Infection, Immunity & Inflammation , University of Glasgow , Glasgow , UK.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D008134:Long-Term Care; D018942:Macrolides / Q000008:administration & dosage / Q000627:therapeutic use; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011812:Quinuclidines / Q000008:administration & dosage / Q000627:therapeutic use; D054852:Small Molecule Libraries / Q000008:administration & dosage / Q000627:therapeutic use*; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; C573971:GSK573719; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020024:Leukotriene Antagonists; D018942:Macrolides; D018727:Muscarinic Antagonists; D058988:Phosphodiesterase 4 Inhibitors; D047428:Protein Kinase Inhibitors; D011812:Quinuclidines; D054852:Small Molecule Libraries; D000069447:Tiotropium Bromide
keywords: Asthma; CRTH2 antagonist; CXCR2 antagonist; inhaled corticosteroid; long-acting beta2-agonist; long-acting muscarinic antagonist; macrolide; modulator; phosphodiesterase inhibitor; protein kinase inhibitor; selective glucocorticoid receptor; statin; theophylline