| Identification | Back Directory | [Name]
N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-Methyl-6-O-Methyl-P-phenyl-5'-guanylyl]- L-alanine 1-Methylethyl ester | [CAS]
1231747-08-2 | [Synonyms]
PSI-353661
N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-Methyl-6-O-Methyl-P-phenyl-5'-guanylyl]- L-alanine 1-Methylethyl ester
L-Alanine, N-[[P(S),2'R]-2'-deoxy-2'-fluoro-2'-methyl-6-O-methyl-P-phenyl-5'-guanylyl]-, 1-methylethyl ester
N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-Methyl-6-O-Methyl-P-phenyl-5'-guanylyl]- L-alanine 1-Methylethyl ester USP/EP/BP | [Molecular Formula]
C24H32FN6O8P | [MDL Number]
MFCD18782729 | [MOL File]
1231747-08-2.mol | [Molecular Weight]
582.52 |
| Hazard Information | Back Directory | [Uses]
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]. | [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].
| Animal Model: | Human hepatocyte chimeric mice infected with HCV | | Dosage: | 50 mg/kg, together with 400 mg/kg of Telaprevir | | Administration: | Oral administration (p.o.) | | Result: | Achieved sustained eradication of the mutant virus or the end-of-treatment response.
Reduced serum levels of HCV RNA.
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| [References]
[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 |
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