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PSI-352938 (PSI-938) is a hepatitis C virus (HCV) nucleotide inhibitor.

PSI-352938 (PSI-938) and PSI-353661 inhibit HCV genotype (GT) 1b replicon replication with 50% effective concentrations (EC50s) of 0.13±0.076 μM and 3.0±1.4 nM, respectively, and are similarly active against GT 1a and 2a replicons and infectious viruses. Metabolism of PSI-352938 and PSI-353661 generates the same 5′-triphosphate metabolite, PSI-352666, which is similarly active against NS5B polymerases from GT 1 to 4[1]. PSI-352938 (PSI-938) is a novel cyclic phosphate prodrug of β-D-2′-deoxy-2′-α-fluoro-2′-β-C-methylguanosine 5′-monophosphate that has potent activity against HCV. PSI-352938 (PSI-938) has similar activity against genotype 1a, 1b, and 2a replicons, with EC50s ranging from 0.13 to 0.20 μM and EC90 values ranging from 0.35 to 0.74 μM. PSI-352938 (PSI-938) also effectively inhibits HCV replication in the infectious virus assays: the EC50 and EC90 values are 0.28±0.083 μM and 0.63±0.018 μM, respectively, against the H77 infectious virus and 0.39±0.31 μM and 1.16±0.64 μM, respectively, against the JFH-1 infectious virus. In contrast, PSI-352938 is not active against HBV or HIV up to the highest concentration tested (EC50>100 μM)[2].

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