Sofosbuvir (PSI-7977, GS-7977)

Catalog No.S2794

Sofosbuvir (PSI-7977, 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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Cited by 7 Publications

3 Customer Reviews

  • Representative confocal microscope image showing phosphorylated Drp1 translocation to mitochondria and mitochondrial fission in the presence of Sofosbuvir. At 24 hours after treatment with Sofosbuvir (100 nM), Huh7 cells were immunostained with antibodies against TOM20 (red) and p-Drp1 (S616) (green). Nuclei are demarcated with white dotted circles. Treated (+) and untreated (–) cells are marked. In the zoomed images, the arrows indicate the colocalization of TOM20 and p-Drp1 (S616) in Sofosbuvir-treated cells (yellow spots).

    Hepatology, 2017, 66(3):758-771. Sofosbuvir (PSI-7977, GS-7977) purchased from Selleck.

    Inhibition of hepatitis C virus by sofosbuvir. (A) Determination of 50% cytotoxic concentration (CC50). Huh-7.5 reporter cells (1.3×104) were incubated with the indicated concentration of sofosbuvir (SOF) during 72 h at 37°C, and the numbers of viable cells were counted using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. (B) Determination of the drug concentration required for 50% inhibition (IC50) of infectious HCV yield. Huh-7.5 reporter cells (1.0×105) were infected with 3 103 TCID50 of HCV p0 in the presence of the indicated concentrations of SOF. Virus titers were determined in the cell culture supernatants at 72 h postinfection. Viral titers are given as the percentages of the titers obtained in the infection in the absence of SOF. (C) Progeny production in the course of three serial passages of HCV p0 in the presence of increasing concentrations of SOF, as indicated. Infection conditions are those explained in the description of panel B. Procedures are detailed in Materials and Methods.

    Antimicrob Agents Chemother, 2016, 60(6):3786-3793.. Sofosbuvir (PSI-7977, GS-7977) purchased from Selleck.

  • Huh-7 cells were inoculated with HCV JFH-1 in the presence of TF3 at given concentrations. Inoculum was removed and replaced by medium containing or not Sofosbuvir at 400 nM. Cells were fixed at 30 h post infection and subjected to immunofluorescent detection of E1 envelope protein. Results are expressed as mean +/- SEM (error bars) of 3 independent experiments performed in triplicate. Data are normalized to DMSO, which is expressed as 100% infection.

    PLoS One, 2018, 13(11):e0198226. Sofosbuvir (PSI-7977, GS-7977) purchased from Selleck.

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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 N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03882307 Not yet recruiting Hepatitis C Chronic Assiut University May 1 2019 Early Phase 1
NCT03882307 Not yet recruiting Hepatitis C Chronic Assiut University May 1 2019 Early Phase 1
NCT03492112 Not yet recruiting Hepatitis C Kirby Institute April 2019 Not Applicable
NCT03492112 Not yet recruiting Hepatitis C Kirby Institute April 2019 Not Applicable
NCT03855917 Not yet recruiting Hepatitis C Kirby Institute April 2019 Phase 4
NCT03855917 Not yet recruiting Hepatitis C Kirby Institute April 2019 Phase 4

Tech Support

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