Sofosbuvir (GS-7977)

For research use only. Not for use in humans.

Catalog No.S2794 Synonyms: PSI-7977

22 publications

Sofosbuvir (GS-7977) Chemical Structure

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.

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Selleck's Sofosbuvir (GS-7977) has been cited by 22 publications

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Biological Activity

Description Sofosbuvir (PSI-7977, GS-7977) is a HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection.
Targets
NS5B polymerase [1]
In vitro

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. [1] 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. [2] 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. [3]

Protocol

Cell Research:[2]
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  • Cell lines: Huh7, HepG2, BxPC3, and CEM
  • Concentrations: Dissolved in DMSO, final concentrations ~100 μM
  • Incubation Time: 8 days
  • Method: Cells are exposed to various concentrations of PSI-7977 for 8 days. At the end of the growth period, MTS dye from the CellTiter 96 AQueous One Solution Cell Proliferation Assay kit is added to each well, and the plate is incubated for an additional 2 hours. The absorbance at 490 nm is read with a Victor3 plate reader using themedium only controlwells as blanks. The 50% inhibition value (IC50) is determined by comparing the absorbance in wells containing cells and PSI-7977 to untreated cell control wells.
    (Only for Reference)

Solubility (25°C)

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)

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 529.45
Formula

C22H29FN3O9P

CAS No. 1190307-88-0
Storage powder
in solvent
Synonyms PSI-7977
Smiles CC(C)OC(=O)C(C)N[P](=O)(OCC1OC(N2C=CC(=O)NC2=O)C(C)(F)C1O)OC3=CC=CC=C3

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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 --

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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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID