GSK984 is an inactive control probe for GSK983, which is an inhibitor of dihydroorotate dehydrogenase (DHODH) with antiviral activity.
GSK984 is an inactive control probe for GSK983, which is an inhibitor of dihydroorotate dehydrogenase (DHODH) with antiviral activity. GSK983 blocks RNA virus replication with EC50 values of 10–40 nM, and also blocks cell proliferation. GSK984 acts by inhibition of dihydroorotate dehydrogenase (DHODH), necesssary for pyrimidine biosynthesis. Exogenous deoxycytidine was able to reduce GSK983 cytotoxicity, allowing cells to synthesize DNA, but still preventing RNA virus replication. GSK983 was active against dengue fever and Venezuelan equine encephalitis viruses. GSK984, the (S)-isomer, is almost 200-fold less active, so would make a good control.
Synthesis of a series of tetrahydrocarbazole amides with potent activity against human papillomaviruses is described. Synthetic approaches allowing for variation of the substitution pattern of the tetrahydrocarbazole and the amide are outlined and resulting changes in antiviral activity and certain
Nature chemical biology, 12(5), 361-366 (2016-03-29)
Broad-spectrum antiviral drugs targeting host processes could potentially treat a wide range of viruses while reducing the likelihood of emergent resistance. Despite great promise as therapeutics, such drugs remain largely elusive. Here we used parallel genome-wide high-coverage short hairpin RNA
GSK983, a novel tetrahydrocarbazole, inhibits the replication of a variety of unrelated viruses in vitro with EC(50) values of 5-20 nM. Both replication of the adenovirus Ad-5 and the polyoma virus SV-40, and episomal maintenance of human papillomaviruses (HPV) and
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