PSI-353661  (Synonyms: GS-558093)

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].

NS5B polymerase^[3]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

PSI-353661 (50 mg/kg, p.o., together with 400 mg/kg of Telaprevir.html" class="link-product" target="_blank">Telaprevir (HY-10235), daily for 4 weeks) is effective against human hepatocyte chimeric mice infected with HCV^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

582.52

C₂₄H₃₂FN₆O₈P

1231747-08-2

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Wonsuk Chang, et al. Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of HCV Infection. ACS Med Chem Lett. 2010 Dec 17;2(2):130-5.  [Content Brief]

  [2]. Furman PA, et al. Activity and the metabolic activation pathway of the potent and selective hepatitis C virus pronucleotide inhibitor PSI-353661. Antiviral Res. 2011 Aug;91(2):120-32.  [Content Brief]

  [3]. Yugo Kai, et al. Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice.  [Content Brief]