Sofosbuvir (PSI-7977, GS-7977)
Molecular Weight(MW): 529.45
Sofosbuvir (PSI-7977, GS-7977) is a HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection.
Cited by 22 Publications
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|Description||Sofosbuvir (PSI-7977, GS-7977) is a HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection.|
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. 
|In vitro||DMSO||100 mg/mL warmed (188.87 mM)|
|Ethanol||100 mg/mL (188.87 mM)|
|Water||11 mg/mL warmed (20.77 mM)|
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03903185||Recruiting||Drug: Ledipasvir / Sofosbuvir Oral Product||Hepatitis C Chronic|Hematologic Malignancy||Ain Shams University|Cairo University||March 1 2019||Phase 1|Phase 2|
|NCT03801707||Recruiting||Drug: Sofosbuvir/Velpatasvir||Kidney Transplant|Hepatitis C|HCV||Ohio State University||January 9 2019||Phase 2|Phase 3|
|NCT03572140||Not yet recruiting||Diagnostic Test: RAVS In relapsed and resistent cases||HCV||Assiut University||July 1 2018||--|
|NCT03639207||Withdrawn||--||Hepatitis C Virus||National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)||June 15 2018||--|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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