Denufosol is a novel second-generation, metabolically stable, selective P2Y(2) receptor agonist. As ion channel regulator denufosol corrects the ion transport defect and increases the overall mucociliary clearance in cystic fibrosis (CF) lung disease by increasing chloride secretion, inhibiting sodium absorption, and increasing ciliary beat frequency in the airway epithelium independently of cystic fibrosis transmembrane conductance regulator genotype. Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. The drug half-life is 25 hours in ex vivo CF sputum and 3 hours when added in vitro to human respiratory epithelial cultures. Denufosol has been generally well-tolerated in healthy volunteers and patients with cystic fibrosis. The most common adverse events were in the respiratory system, with cough having the highest frequency.

Idoxuridine is an antiviral agent use in keratitis caused by herpes simplex virus. As a prescription drug it comes as a 0.1% ophthalmic solution/drops (Herplex and Dendrid). The first studies of the compound for treatment of human herpes simplex started in early 1960s. Being a structural analog of thymidine idoxuridine inhibits viral DNA replication by substituting thymidine. The effect of idoxuridine results in the inability of the virus to reproduce and/or infect tissues. Idoxuridine also blocks viral thymidine kinase as its substrate analog.

Uridine 5'-triphosphate (UTP, INS316) is a naturally occurring agonist for P2Y(2) receptors on the apical surface of ciliated respiratory epithelium. INS316, being developed by Inspire Pharmaceuticals, is a short-acting, aerosolized uridine 5-triphosphate (UTP) solution used as a diagnostic aid for lung cancer. INS316 appears to improve sputum expectoration mediated through the P2Y2 receptor, a nucleotide receptor expressed in human airway epithelial cells and some other tissues. UTP binding to the P2Y2 receptor triggers signal transduction that leads to chloride ion secretion, thereby resulting in mucociliary clearance of airway. UTP stimulates salt and water transport and cilia beat frequency in human airway epithelium in vitro. Single, inhaled doses of UTP stimulate mucociliary clearance in conscious, intubated sheep and in patients with mild chronic bronchitis (smokers and former smokers), suggesting that UTP may be useful for obtaining deep-lung sputum specimens suitable for diagnostic purposes. A single dose of INS316 safely improves the ability of patients with mild chronic bronchitis to expectorate a deep-lung sputum specimen suitable for cytologic evaluation.