Sofosbuvir (PSI-7977, GS-7977) 1190307-88-0

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Molecular Weight:

529.45 Sofosbuvir (PSI-7977, GS-7977) is a HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection.

Biological Activity

As HCV NS5B polymerase inhibitor, PSI-7977 displays more potent
inhibitory activity against HCV RNA replication than PSI-7976 with EC50
of 92 nM versus 1.07 μM and EC90 of 0.29 μM versus 2.99 μM, consistent
with that incubating clone A cells with PSI-7977 leads to a higher
concentration of PSI-7409 than clone A cells incubated with PSI-7976.


PSI-7977 is an effective substrate for CatA to form PSI-352707 with
18-30 fold more potency as compared with PSI-7976. Unlike GS-7976,
however, the CES1-mediated hydrolysis of PSI-7977 does not progress in a
time-dependent manner. The S282T NS5B polymerase
mutation but not S96T mutation confers resistance to PSI-7977 with EC90
increases from 0.42 μM to 7.8 μM. When assessed in an 8-day cytotoxicity
assay, PSI-7977 displays no cytotoxicity against Huh7, HepG2, BxPC3,
and CEM cells even at concentrations up to 100 μM.


PSI-7977 treatment
for 14 days shows a IC90 of 72.1 μM and 68.6 μM for the inhibition of
mtDNA and rDNA, respectively, in HepG2 cells. PSI-7977
exhibits potent activity against genotype (GT) 1a, 1b, and 2a (strain
JFH-1) replicons and chimeric replicons containing GT 2a (strain J6),
2b, and 3a NS5B polymerase. Sequence analysis of the JFH-1 NS5B region
indicates that additional amino acid changes including T179A, M289L,
I293L, M434T, and H479P are selected both prior to and after the
emergence of S282T, which are required to confer resistance to PSI-7977.

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Product Categories : DNA Damage > DNA/RNA Synthesis Inhibitor