| Description |
RO-9187 is a potent inhibitor of HCV virus replication with an IC50 of 171 nM.
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| Related Catalog |
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| Target |
IC50: 171 nM (HCV)[1]
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| In Vitro |
RO-9187 is excellent substrates for deoxycytidine kinase and is phosphorylated with efficiencies up to 3-fold higher than deoxycytidine. RO-9187 inhibits RNA synthesis by HCV polymerases from either HCV genotypes 1a and 1b or containing S96T or S282T point mutations with similar potencies, suggesting no cross-resistance with either R1479 (4′-azidocytidine) or 2′-C-methyl nucleosides. The formation of RO-9187-TP increased in a time- and dose-dependent manner. The maximal triphosphate concentration at 24 h is 87 pmol/106 cells with half-maximal triphosphate formation achieved at 12 μM RO-9187[1].
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| In Vivo |
Plasma exposures of RO-9187 in rats increase in a dose-dependent manner between 10 and 2000 mg/kg after oral dosing. Plasma concentrations of 1.4 and 26 μM (390 and 7454 ng/mL) are achieved in rats and dogs at the 10 mg/kg dose level, respectively. Plasma concentrations up to 57 μM are achieved in rats dosed with 2000 mg/kg/day[1].
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| Animal Admin |
Rats: A 2-week oral range finding toxicity study is performed with RO-9187 and ribavirin in Hanover-Wistar rats. Five male and five female rats in each of five treatment groups are administered once daily doses of vehicle, 200, 600, or 2000 mg/kg RO-9187 or 200 mg/kg ribavirin by oral gavage for 14 days[1].
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| References |
[1]. Klumpp K, et al. 2'-deoxy-4'-azido nucleoside analogs are highly potent inhibitors of hepatitis C virus replication despite the lack of 2'-alpha-hydroxyl groups. J Biol Chem. 2008 Jan 25;283(4):2167-75.
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