Lihlahisoa

Beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) ke inhibitor e khethehileng ea hepatitis C virus (HCV) RNA synthesis ka Huh-7 replicon cell.Ho thibela HCV NS5B RNA polymerase, PSI-6130 e tlameha ho ba phosphorylated ho foromo ea 5'-triphosphate.Phosphorylation ea PSI-6130 le inhibition ea HCV NS5B li ile tsa fuputsoa.Phosphorylation ea PSI-6130 ka recombinant human 2'-deoxycytidine kinase (dCK) le uridine-cytidine kinase 1 (UCK-1) e ile ea lekanyetsoa ka ho sebelisa mokhoa o kopanetsoeng oa spectrophotometric.PSI-6130 e bontšitsoe e le substrate bakeng sa dCK e hloekisitsoeng, e nang le Km ea 81 microM le kcat ea 0.007 s-1, empa e ne e se substrate bakeng sa UCK-1.PSI-6130 monophosphate (PSI-6130-MP) e ne e entsoe ka phosphorylated hantle ho diphosphate mme hamorao ho triphosphate ka recombinant UMP-CMP kinase ea motho le nucleoside diphosphate kinase, ka ho latellana.Thibelo ea mefuta e hlaha le e fetotsoeng (S282T) HCV NS5B RNA polymerase e ile ea ithutoa.The steady-state inhibition constant (Ki) bakeng sa PSI-61 30 triphosphate (PSI-6130-TP) e nang le enzyme ea mofuta o hlaha e ne e le 4.3 microM.Liphetho tse tšoanang li ile tsa fumanoa ka 2'-C-methyladenosine triphosphate (Ki = 1.5 microM) le 2'-C-methylcytidine triphosphate (Ki = 1.6 microM).NS5B e nang le phetoho ea S282T, e tsejoang ka ho fana ka khanyetso ho 2'-C-methyladenosine, e ne e thibetsoe ke PSI-6130-TP ka katleho joaloka mofuta o hlaha.Ho kenyelletsoa ha PSI-6130-MP ho RNA e hlahisitsoeng ke NS5B RNA polymerase e hloekisitsoeng ho felletse ka ho felisoa ha ketane.