Denufosol

Source: Wikipedia, the free encyclopedia.
Denufosol
Denufosol tetrasodium
Clinical data
Other namesINS37217
2'-Desoxycytidine (5')tetraphospho(5')uridine
Routes of
administration		Inhalation
ATC code
  • none
Legal status
Legal status
  • Investigational
Identifiers
  • [[(3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate
JSmol)
  • C1[C@@H]([C@H](O[C@H]1N2C=CC(=NC2=O)N)COP(=O)(O)OP(=O)(O)OP(=O)(O)OP(=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)N4C=CC(=O)NC4=O)O)O)O
  • InChI=1S/C18H27N5O21P4/c19-11-1-3-22(17(28)20-11)13-5-8(24)9(40-13)6-38-45(30,31)42-47(34,35)44-48(36,37)43-46(32,33)39-7-10-14(26)15(27)16(41-10)23-4-2-12(25)21-18(23)29/h1-4,8-10,13-16,24,26-27H,5-7H2,(H,30,31)(H,32,33)(H,34,35)(H,36,37)(H2,19,20,28)(H,21,25,29)/t8-,9+,10+,13+,14+,15+,16+/m0/s1
  • Key:FPNPSEMJLALQSA-MIYUEGBISA-N
  (verify)

Denufosol (

FEV1 (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 of retinal detachment and other retinal diseases, but trials were terminated in 2006.[3]

Application

In Phase III studies, denufosol was orally inhaled by patients with cystic fibrosis three times a day using a jet nebulizer. 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]

Mechanism of action

Cystic fibrosis is characterised by a defect of the

P2Y2 subtype of purinergic 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]

Chemistry

Denufosol consists of two nucleosides (composed of a nucleobase and a sugar each), deoxycytidine and uridine, linked on their sugars by four units of phosphoric acid. It is used in form of its tetrasodium salt.[citation needed]

References

  1. PMID 21169471
    .
  2. ^ "Inspire Announces Results of Second Phase 3 Trial with Denufosol for Cystic Fibrosis". Archived from the original on 2012-03-22. Retrieved 2011-04-03.
  3. ^ Clinical trial number NCT00083967 for "Study of Denufosol (INS37217) in Subjects With Rhegmatogenous Retinal Detachment" at ClinicalTrials.gov
  4. ^ Spreitzer H (14 March 2011). "Neue Wirkstoffe – Denufosol". Österreichische Apothekerzeitung (in German) (6/2011): 10.
  5. PMID 18276176
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Denufosol&oldid=1149327930"