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Sofosbuvir (PSI-7977)

Cat. No. M3666
Sofosbuvir (PSI-7977) Structure

Sofosbuvir, GS-7977

Size Price Availability Quantity
10mg USD 61.2  USD68 In stock
25mg USD 72  USD80 In stock
50mg USD 81  USD90 In stock
100mg USD 99  USD110 In stock
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Quality Control
Biological Activity

PSI-7977 (sofosbuvir) is an investigational nucleotide analog for treatment of chronic HCV infection. PSI-7977 (GS-7977) is a uridine nucleotide analog as HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. PSI-7977 is a more potent inhibitor of HCV RNA replication than PSI-7976. When CatA is incubated with PSI-7977 or PSI-7976, ~18-fold more PSI-352707 is formed when PSI-7977 is the substrate compared with PSI-7976, and the catalytic efficiency for PSI-7977 with CatA is ~30-fold higher than that for PSI-7976. However, CES1 preferentially hydrolyzes PSI-7976 over PSI-7977. Incubating clone A cells with PSI-7977 results in a higher concentration of PSI-7409 than that with PSI-7976. NS5B polymerase S282T mutation but not S96T mutation is resistant to PSI-7977 with EC90 of 7.8 μM. PSI-7977 has no cytotoxicity against Huh7, HepG2, BxPC3, and CEM cells even at concentrations up to 100 μM. PSI-7977 is active against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Cross-resistance studies using GT 1b replicons confirme that the S282T change conferres resistance to PSI-7977. Data from the JFH-1 replicon variants show that amino acid changes within the finger and palm domains together with S282T are required to confer resistance to PSI-7977, while the mutations on the thumb domain serve to enhance the replication capacity of the S282T replicons. PSI-7977 is currently being investigated in phase 3 clinical trials for the treatment of hepatitis C.

Cell Experiment
Cell lines Huh7, HepG2, BxPC3, and CEM
Preparation method Exposing cells to various concentrations of PSI-7977 for 8 days. At the end of the growth period, adding MTS dye from the CellTiter 96 AQueous One Solution Cell Proliferation Assay kit to each well, and incubating the plate for an additional 2 hours. Read the absorbance at 490 nm with a Victor3 plate reader using themedium only controlwells as blanks. determing the 50% inhibition value (IC50) by comparing the absorbance in wells containing cells and PSI-7977 to untreated cell control wells.
Concentrations Dissolved in DMSO, final concentrations ~100 μM
Incubation time 8 days
Animal Experiment
Animal models
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 529.45
Formula C22H29FN3O9P
CAS Number 1190307-88-0
Purity >99%
Solubility DMSO 80 mg/mL
Water 9 mg/mL
Storage at -20°C

Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus.
Lam AM1, et al. Antimicrob Agents Chemother. 2012 Jun;56(6):3359-68. PMID: 22430955.

Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938.
Chun BK, et al. Nucleosides Nucleotides Nucleic Acids. 2011 Nov;30(11):886-96. PMID: 22060553.

Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus.
Sofia MJ, et al. J Med Chem. 2010 Oct 14;53(19):7202-18. PMID: 20845908.

Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977.
Murakami E, et al. J Biol Chem. 2010 Nov 5;285(45):34337-47. PMID: 20801890.

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Keywords: Sofosbuvir (PSI-7977), Sofosbuvir, GS-7977 supplier, HCV Protease, inhibitors

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