Filibuvir

Filibuvir (also known as PF-00868554, PF-868554) was a non-nucleoside orally available[1] NS5B inhibitor developed by Pfizer for the treatment of hepatitis C. It binds to the non-catalytic Thumb II allosteric pocket of NS5B viral polymerase and causes a decrease in viral RNA synthesis. It is a potent and selective inhibitor, with a mean IC50 of 0.019 μM against genotype 1 polymerases.[2] Several filibuvir-resistant mutations have been identified, M423 being the most common that occurred after filibuvir monotherapy.[3] It was intended to be taken twice-daily.[4]

Filibuvir
Clinical data
Other namesPF-00868554
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • Development terminated
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC29H37N5O3
Molar mass503.647 g·mol−1
3D model (JSmol)

Its investigation was discontinued on February 2013 due to strategic reasons.[5][6]

References

  1. "Pfizer Halts Development of Hepatitis C Drug Filibuvir: Report". FirstWorld Pharma. Doctor's Guide Publishing Limited. Retrieved 5 December 2015.
  2. Shi ST, Herlihy KJ, Graham JP, Nonomiya J, Rahavendran SV, Skor H, et al. (June 2009). "Preclinical characterization of PF-00868554, a potent nonnucleoside inhibitor of the hepatitis C virus RNA-dependent RNA polymerase". Antimicrobial Agents and Chemotherapy. 53 (6): 2544–52. doi:10.1128/AAC.01599-08. PMC 2687230. PMID 19307358.
  3. Jiao P, Xue W, Shen Y, Jin N, Liu H (April 2014). "Understanding the drug resistance mechanism of hepatitis C virus NS5B to PF-00868554 due to mutations of the 423 site: a computational study". Molecular BioSystems. 10 (4): 767–77. doi:10.1039/c3mb70498j. PMID 24452008.
  4. Beaulieu PL (December 2010). "Filibuvir, a non-nucleoside NS5B polymerase inhibitor for the potential oral treatment of chronic HCV infection". IDrugs. 13 (12): 938–48. PMID 21154154.
  5. Loftus P (8 March 2013). "Pfizer Stops Developing Hepatitis C Drug". The Wall Street Journal. Dow Jones & Company, Inc. Retrieved 5 December 2015.
  6. Gentile I, Buonomo AR, Zappulo E, Borgia G (February 2015). "Discontinued drugs in 2012 - 2013: hepatitis C virus infection". Expert Opinion on Investigational Drugs. 24 (2): 239–51. doi:10.1517/13543784.2015.982274. PMID 25384989.
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