title: Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease.
abstract: P2Y(2) receptor agonists are a new class of compounds that are being evaluated as a treatment for the pulmonary manifestations of Cystic Fibrosis (CF). Results of preclinical research suggest that these compounds inhibit sodium absorption, restore chloride conductance and rehydrate the CF airway surface. In addition, P2Y(2) receptor agonists have been shown to enhance ciliary beat frequency and increase mucociliary clearance in animals and subjects with impaired mucociliary clearance. The normalization of airway surface liquid and enhancement of lung clearance is expected to provide a clinical benefit to CF patients. A number of P2Y(2) agonist compounds have been evaluated in healthy subjects and patients with CF. Most recently, INS37217, a metabolically stable and potent P2Y(2) agonist has been developed and studies have shown it to be well-tolerated when given via inhalation. This compound is currently being evaluated in children and adults with CF lung disease.
authors.affiliation: Inspire Pharmaceuticals, Inc, Durham, NC 27709, USA. k@inspirepharm.com
authors.forename: Don
authors.initials: D
authors.lastname: Kellerman
authors.forename: Richard
authors.initials: R
authors.lastname: Evans
authors.forename: Dave
authors.initials: D
authors.lastname: Mathews
authors.forename: Christy
authors.initials: C
authors.lastname: Shaffer
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004848:Epithelium / Q000503:physiopathology; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D014500:Uracil Nucleotides; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D003845:Deoxycytosine Nucleotides; D009883:Ophthalmic Solutions; C546385:P2RY2 protein, human; D011122:Polyphosphates; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D014500:Uracil Nucleotides; C403315:diquafosol; C465279:denufosol tetrasodium; D014529:Uridine