Potent hepatitis C virus (HCV) replication inhibitor (EC50 = 35 nM). Is rapidly metabolized in primary human hepatocytes to 2'-C-methyl guanosine triphosphate, an inhibitor of HCV RNA-dependent RNA polymerase NS5b. Displays 10-fold reduction in potency in S282T mutant-expressing versus wild-type replicons. Exhibits synergy with Ribavirin . Orally bioavailable.
Vernachio et al (2011) INX-08189, a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob.Agents Chemother. 55 1843 PMID:21357300 |McGuigan et al (2010) Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus. Bioorg.Med.Chem.Lett. 20 4850 PMID:20637609