R-7128

Mericitabine (R-7128) is a nucleoside inhibitor of the HCV NS5B polymerase that acts as an RNA chain terminator and prevents elongation of RNA transcripts during replication.

Signaling Pathways >> Metabolic Enzyme/Protease >> HCV Protease

Signaling Pathways >> Anti-infection >> HCV

Research Areas >> Infection

HCV NS5B polymerase[1]

Mericitabine (R-7128) is an oral prodrug of PSI-6130, a cytidine analogue. Pre-clinical observations demonstrated that PSI-6130 has an EC90 value of 4.6±2 μM in the HCV replicon assay. Mericitabine shows high specificity for HCV, minimal cytotoxicity and does not affect mitochondrial DNA. PSI-6130 is converted through phosphorylation by cellular kinases to an active 5′-triphosphate metabolite, which inhibits the NS5B RNA polymerase of HCV. Mericitabine demonstrates a relatively good safety profile and significant potency against HCV-1[2]. Mericitabine is a first-in class nucleoside polymerase inhibitor (NPI), which requires intracellular uptake and phosphorylation to two active triphosphates. R-7128 is an oral cytidine nucleoside analog prodrug that exhibits strong antiviral effectiveness against the HCV polymerase across all HCV genotypes[3].

[1]. Le Pogam S, et al. Characterization of HCV quasispecies dynamics upon short term dual-therapy with the HCV NS5B nucleoside polymerase inhibitor mericitabine and the NS3/4 protease inhibitor danoprevir. Antimicrob Agents Chemother. 2012 Nov;56(11):5494-5

[2]. Soriano V, et al. Directly acting antivirals against hepatitis C virus. J Antimicrob Chemother. 2011 Aug;66(8):1673-86

[3]. Guedj J, et al. Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128). Hepatology. 2012 Apr;55(4):1030-7.

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