Qi Liu, Amita Gupta, Ayse Okesli-Armlovich, Wenjie Qiao, Curt R. Fischer, Mark Smith, Jan E. Carette, Michael C. Bassik, Chaitan Khosla
Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase (DHODH) as its target, along with the discovery that knockdown of genes in pyrimidine salvage pathways sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor…
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