In vitro
As a nonnucleoside inhibitor, VX-222 (VCH-222) can potently and selectively inhibit HCV polymerase with IC50 of 0.94-1.2 uM. VX-222 binds to the HCV polymerase with dissociation constants of 17 nM. VX-222 can inhibit HCV replication via NS5B (polymerase of hepatitis C virus).VX-222 interfered with the interaction between NS5B and RNA. VX-222 inhibited the 1b/Con1 HCV subgenomic replicon, with EC50 of 5 nM. The inhibitory activity of VX-222 was only modestly affected by the M423T substitution but more significantly affected by an I482L substitution.
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