Author: Qi Liu; Amita Gupta; Ayse Okesli-Armlovich; Wenjie Qiao; Curt R. Fischer; Mark Smith; Jan E. Carette; Michael C. Bassik; Chaitan Khosla
Title: Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism Document date: 2020_3_25
ID: 1zk64gsg_7
Snippet: Our search for lead inhibitors of pyrimidine salvage was inspired by earlier reports on the biological activity of CPU and cyclopentenyl cytosine (CPC), which were shown to block uridine salvage in vitro and in vivo (Cysyk et al., 1995; Lim et al., 1984; Moyer et al., 1985; Schimmel et al., 2007) . In these and other reports, CPU was found to be remarkably well-tolerated, whereas CPC was considerably more cytotoxic (Blaney et al., 1992; Ford et a.....
Document: Our search for lead inhibitors of pyrimidine salvage was inspired by earlier reports on the biological activity of CPU and cyclopentenyl cytosine (CPC), which were shown to block uridine salvage in vitro and in vivo (Cysyk et al., 1995; Lim et al., 1984; Moyer et al., 1985; Schimmel et al., 2007) . In these and other reports, CPU was found to be remarkably well-tolerated, whereas CPC was considerably more cytotoxic (Blaney et al., 1992; Ford et al., 1991; Song et al., 2001) . This contrast is likely due to downstream inhibition of the CTP synthetase by CPC (Schimmel et al., 2007) .
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