Denufosol

Denufosol (INN) is an inhalable drug for the treatment of cystic fibrosis, being developed by Inspire Pharmaceuticals and sponsored by the Cystic Fibrosis Foundation. It has been tested in a number of Phase III clinical trials, initially with good outcomes, but ultimately showing non-significant results compared with placebo.

The drug was also investigated for the treatment of retinal detachment and other retinal diseases, but trials were terminated in 2006.

Application
The substance was applied three times a day with an inhaler ("jet nebulizer"). To be effective, it had to reach the deeper parts of the lung (bronchioles), making it unsuitable for litte children under about five years of age.

Mechanism of action
Cystic fibrosis is characterised by a defect of the chloride channel CFTR (cystic fibrosis transmembrane conductance regulator) on epithelial cells in the lungs. This channel is necessary to regulate the components of sweat, digestive juices, and mucus. Defects lead to a viscous, dehydrated mucus, hindering mucociliary clearance. Denufosol is an agonist at the P2Y2 subtype of purinergic receptors, opening an alternative chloride channel and so partly compensating the effects caused by the non-working CFTR.

Chemistry
Denufosol consists of two nucleosides (composed of a nucleobase and a sugar each), 2'-desoxycytidine and uridine, linked by four units of phosphoric acid. It is used in form of its tetrasodium salt.