[HTML][HTML] Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977
E Murakami, T Tolstykh, H Bao, C Niu… - Journal of biological …, 2010 - ASBMB
A phosphoramidate prodrug of 2′-deoxy-2′-α-fluoro-β-C-methyluridine-5′-
monophosphate, PSI-7851, demonstrates potent anti-hepatitis C virus (HCV) activity both in
vitro and in vivo. PSI-7851 is a mixture of two diastereoisomers, PSI-7976 and PSI-7977,
with PSI-7977 being the more active inhibitor of HCV RNA replication in the HCV replicon
assay. To inhibit the HCV NS5B RNA-dependent RNA polymerase, PSI-7851 must be
metabolized to the active triphosphate form. The first step, hydrolysis of the carboxyl ester by …
monophosphate, PSI-7851, demonstrates potent anti-hepatitis C virus (HCV) activity both in
vitro and in vivo. PSI-7851 is a mixture of two diastereoisomers, PSI-7976 and PSI-7977,
with PSI-7977 being the more active inhibitor of HCV RNA replication in the HCV replicon
assay. To inhibit the HCV NS5B RNA-dependent RNA polymerase, PSI-7851 must be
metabolized to the active triphosphate form. The first step, hydrolysis of the carboxyl ester by …