PSI-7409 tetrasodium is an active 5'-triphosphate metabolite, inhibiting HCV NS5B polymerases, with IC
50
s of 1.6, 2.8, 0.7 and 2.6 μM for GT 1b_Con1, GT 2a_JFH1, GT 3a, and GT 4a NS5B polymerases, respectively. PSI-7409 also weakly inhibits human DNA polymerase α, with an IC
50
of 550 μM, but shows no inhibition on DNA Pol β and γ. In clone A cells, the levels of PSI-7409 gradually increases to a maximum concentration of about 25 μM over a period of 48 h. PSI-7409 forms at a much faster rate in primary human hepatocytes, achieving a maximum intracellular concentration of ∼100 μM at 4 h and remains at that concentration for 48 h.
