Maribavir

Maribavir, also known as 1263W-94; BW-1263W-94; GW-1263; GW-257406X; SHP-620; VP-41263; BW-1263W94, is an UL97 kinase inhibitor potentially for the treatment of cytomegalovirus (CMV) infection. The mechanism by which maribavir inhibits HCMV replication is by inhibition of an HCMV encoded protein kinase enzyme called UL97 or pUL97. (In Vitro) :Maribavir is a potent inhibitor of the autophosporylation of the wild type and all the major Ganciclovir (GCV) resistant UL97 mutants analysed with a mean IC50 of 35 nM. The M460I mutation results in hypersensitivity to Maribavir with an IC50 of 4.8 nM. A Maribavir resistant mutant of UL97 (L397R) is functionally compromised as both a Ganciclovir kinase and a protein kinase (~ 10% of wild type levels) . Enzyme kinetic experiments demonstrate that Maribavir is a competitive inhibitor of ATP with a Ki of 10 nM. Maribavir (1263W94) inhibits viral replication in a dose-dependent manner, with IC50 of 0.12±0.01 μM as measured by a multicycle DNA hybridization assay. The pUL97 protein kinase is strongly inhibited by Maribavir, with 50% inhibition occurring at 3 nM.