Denufosol Tetrasodium P2Y2 Agonist Treatment of Cystic Fibrosis

Cystic fibrosis (CF) is a disease with a low life expectancy and a range of morbidities that result from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. In recent years, investigation has increasingly focused on treating the underlying causes of the disease instead of their downstream effects. One promising approach is to correct abnormal ion transport defects in airways via P2Y(2) receptor agonism. One such compound is denufosol tetrasodium (INS-37217), which demonstrated a preclinical pharmacological profile similar to the natural P2Y(2) receptor ligand uridine 5'-triphosphate (UTP), increasing chloride and water secretion, ciliary beat frequency and mucin release. In vivo enhancement of mucus transport has also been seen, with the agent displaying a notably enhanced duration of action. Denufosol has been safe and well tolerated in clinical studies to date and has demonstrated potentially beneficial effects, including improvements in lung function in CIF patients enrolled in a phase II study.