idx184

IDX184 is a potent, orally active, targeted HCV polymerase inhibitor and nucleoside polymerase.IDX184 effectively inhibits HCV polymerase (IC50=0.31 μM, Ki=52.3 nM). IDX184 is a liver-targeted nucleotide prodrug with anti-HCV activity that inhibits HCV NS5B polymerase and can be used in combination with pegylated interferon-α2a and ribavirin for the primary treatment of chronic hepatitis C. It has been shown to inhibit HCV polymerase and nucleoside polymerase.

2’-O-Methylguanosine-5’-O-triphosphate (2’-methyl GTP) acts as an inhibitor targeting the hepatitis C virus (HCV) non-structural protein 5B (NS5B; with an IC50 of 3.5 µM), and serves as an active metabolite of the prodrug IDX184 through a 2’-methylguanosine intermediate transformation. Additionally, at a concentration of 50 µM, it promotes tubulin polymerization. Notably, levels of 2’-methyl GTP are reduced in the tumoral tissues of patients with hepatocellular carcinoma in comparison to the adjacent normal tissues.