1231747-08-2

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].

[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. DOI:10.1021/ml100209f
[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. DOI:10.1016/j.antiviral.2011.05.003
[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. DOI:10.1007/s00535-015-1108-6