PSI-353661

PSI-353661 (GS-558093) is a purine nucleotide NS5B polymerase inhibitor against HCV infection. PSI-353661 shows EC₉₀s of 8 nM and 11 nM for wild type and S282T resistant replicons of HCV. PSI-353661 can produce high concentrations of the active triphosphate in primary human hepatocytes^[1][3]. IC50 & Target:NS5B polymerase^[3] In Vitro:PSI-353661 exhibits strong inhibition of HCV in the cell-based replicon assay, with EC₉₀s of 8 nM and 11 nM for wild type and S282T resistant replicons^[1].
PSI-353661 (24 h) produces high concentrations of (0.44 mM) triphosphate (TP) level in primary human hepatocytes^[1].
PSI-353661 (4 days) inhibits viral replication with EC₅₀ and EC₉₀ value of 0.0030 μM and 0.0085 μM for genotype 1b replicon cells^[2].
PSI-353661 (8 days) shows little cytotoxicity in Huh7, HepG2, BxPC3, and CEM cells, with IC₅₀ more than 80 μM^[2].
PSI-353661 (8-160 nM, 2 weeks) clears HCV replicon RNA and prevents viral rebound^[2].
In Vivo:PSI-353661 (50 mg/kg, p.o., together with 400 mg/kg of Telaprevir (HY-10235), daily for 4 weeks) is effective against human hepatocyte chimeric mice infected with HCV^[3].