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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  • 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.

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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)
In vivo Add solvents individually and in order:

* 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
NCT02339038 Active, not recruiting HCV HIV National Institutes of Health Clinical Center (CC) January 7, 2015 Phase 4
NCT02985281 Enrolling by invitation Pharmacological Action National Liver Institute, Egypt|Pharco Pharmaceuticals December 2016 Phase 2|Phase 3
NCT02992457 Recruiting Hepatitis C Tanta University December 2016 Phase 4
NCT02858180 Recruiting Hepatitis C, Chronic|Heart Failure|Pulmonary Disease, Chronic Obstructive|Lung Diseases, Interstitial Duke University|Gilead Sciences December 2016 Phase 4
NCT02939989 Enrolling by invitation Hepatitis C Virus Infection AbbVie November 2016 Phase 3
NCT02959359 Not yet recruiting Hepatocellular Carcinoma Taipei Veterans General Hospital, Taiwan|Kaohsiung Medical University Chung-Ho Memorial Hospital|China Medical University Hospital|Chi Mei Medical Hospital|Chiayi Christian Hospital|National Taiwan University Hospital|Chang Gung Memorial Hospital|Tri-Service General Hospital|National Cheng-Kung University Hospital November 2016 Phase 4

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID