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| Other names | INS37217 2'-Desoxycytidine (5')tetraphospho(5')uridine |
| Routes of administration | Inhalation |
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| Formula | C18H27N5O21P4 |
| Molar mass | 773.323 g·mol−1 |
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Denufosol (INN) is an inhaleddrug for the treatment ofcystic fibrosis, being developed byInspire Pharmaceuticals and sponsored by theCystic Fibrosis Foundation. It was tested in two Phase IIIclinical trials, TIGER-1 and TIGER-2. Initially, in the first Phase III trial, TIGER-1, the compound showed significant results as compared withplacebo.[1] In the second Phase III trial, TIGER-2, the compound did not meet the primary endpoint, a significant change in baselineFEV1 (forced expiratory volume in one second) at the week 48 endpoint as compared to placebo.[2] As of 2011, no additional clinical studies are being conducted with the compound.
The drug was also investigated for the treatment ofretinal detachment and otherretinal diseases, but trials were terminated in 2006.[3]
In Phase III studies, denufosol was orally inhaled by patients with cystic fibrosis three times a day using a jetnebulizer. To be effective, it had to reach the deeper parts of the lung (bronchioles), making it unsuitable for children under five years of age.[4]
Cystic fibrosis is characterised by a defect of thechloride channelCFTR (cystic fibrosis transmembrane conductance regulator) onepithelial cells in the lungs. The CFTR regulates the components of sweat, digestive juices, andmucus. Defects lead to aviscous,dehydrated mucus, hinderingmucociliary clearance. Denufosol is anagonist at theP2Y2 subtype ofpurinergic receptors which via its associated G protein leads to activation of alternative chloride channel. Activating this alternate chloride channel theoretically increases ion transport in cystic fibrosis patients which compensates the effects caused by the non-functioning CFTR.[5]
Denufosol consists of twonucleosides (composed of anucleobase and a sugar each),deoxycytidine anduridine, linked on their sugars by four units ofphosphoric acid. It is used in form of its tetrasodium salt.[citation needed]
