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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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

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
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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 (188.87 mM) warming
Ethanol 100 mg/mL (188.87 mM)
Water 11 mg/mL warmed (20.77 mM)
In vivo

* 1 mg/ml means slightly soluble or insoluble.
* 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
NCT02705534 Not yet recruiting Hepatitis C|Cirrhosis Tehran University of Medical Sciences|Bakhtar Bioshimi Co September 2016 Phase 3
NCT02683005 Not yet recruiting Hepatitis C|Pregnancy University of Pittsburgh|Gilead Sciences|University of Nebraska July 2016 Phase 1
NCT02631772 Recruiting Hepatitis C Medical University of South Carolina June 2016 Phase 4
NCT02786537 Recruiting Chronic Hepatitis C University of Florida|Patient-Centered Outcomes Research Institute|Merck Sharp & Dohme Corp.|AbbVie June 2016 Phase 4
NCT02772744 Not yet recruiting Hepatitis C Zagazig University|Cairo University June 2016 --
NCT02781649 Not yet recruiting End-Stage Renal Disease|Hepatitis C Johns Hopkins University|Merck Sharp & Dohme Corp. June 2016 Phase 1

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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