Intracellular metabolism, cytotoxicity (CC50), anti-HCV replicon activity (EC50) and anti-NS5B activity (IC50)a.
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aValues rounded to two significant figures. All values are the mean ± s.d. of at least 3 independent experiments done in duplicate or triplicate except for CC50 Huh-7 for 3-deazaadenosine and 6-methylpurine-riboside, which are the average of replicate wells from one experiment.bIntracellular metabolism [TP] is the amount of nucleoside triphosphate determined from LC/MS/MS analysis and converted from pmol per million cells to intracellular concentration (µM) using a cellular volume of 2 pL per cell. All data for 10 µM 24 h incubations except where noted otherwise.cCompounds that showed toxicity in MT4 cells at 10 µM. Incubations were done at 0.1 µM and the intracellular levels dose normalized assuming proportional increase in intracellular metabolites with extracellular concentrations.dnot determined.eTested in the form of monophosphate prodrug GS-7977.
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2015-12-02



