Description
Filibuvir is an orally active, selective non-nucleoside inhibitor of the HCV nonstructural 5B protein (NS5B) RNA-dependent RNA polymerase (RdRp). Filibuvir binds noncovalently in the thumb II allosteric pocket of NS5B. Filibuvir inhibits genotype 1a and 1b replicons with EC 50 s of 59 nM for both isoforms, respectively. Filibuvir preferentially inhibits elongative RNA synthesis and potently decreases viral RNA accumulation. In VitroFilibuvir (0.01-10000 nM; 48 h) inhibits the WT 1b replicon in a dose-dependent manner, with an EC 50 of ∼70 nM in Huh7.5 cells harboring the HCV replicon. Filibuvir binds to the HCV polymerase with a dissociation constant of 29 nM. Filibuvir preferentially inhibits elongative RNA synthesis rather than de novo-initiated RNA synthesis. Filibuvir has no obvious effect on de novo-initiated RNA synthesis (IC 50 =∼5 µM) but decreases primer extension from PE46, with an IC 50 of 73 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:Solid