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VX-222

Cat. No. M3512
VX-222 Structure
Synonym:

VCH-222, Lomibuvir

Size Price Availability Quantity
5mg USD 115  USD115 In stock
10mg USD 215  USD215 In stock
50mg USD 650  USD650 In stock
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Quality Control & Documentation
Biological Activity

VX-222 is a small molecule non-nucleoside inhibitor of HCV NS5B polymerase that is being investigated for the treatment of hepatitis C virus infection. While the protease inhibitors (telaprevir and boceprevir) are the directly-targeted anti-HCV agents furthest along in the development pipeline, HCV polymerase - an enzyme responsible for copying viral genetic material-is also a promising target. VX-222 is a novel non-nucleoside HCV NS5B polymerase inhibitor with potent in vitro activity.

Protocol (for reference only)
Cell Experiment
Cell lines Huh7.5 cells
Preparation method Trypsinizing Huh7.5 cells harboring HCV RNA replicons and plating into 48-well plates at a concentration of 4 × 104 cells/well. Changing the medium and adding VX-222in 200 μL of complete medium the next day. 48 hours later, total RNA is extracted and viral RNAs are quantified by real-time reverse transcription-PCR (RT-PCR). The effective drug concentrations that reduced HCV RNA replicon levels by 50% (EC50) are calculated by nonlinear regression analysis with log curve fitting
Concentrations 0.01 nM -10 μM
Incubation time 48 hours
Animal Experiment
Animal models Rats or dogs
Formulation Dissolved in 30% PEG
Dosages 5 mg/kg for rats or 10 mg/kg for dogs
Administration By oral gavage
Chemical Information
Molecular Weight 445.61
Formula C25H35NO4S
CAS Number 1026785-59-0
Solubility (25°C) DMSO 80 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
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.

References

[1] Kawthar Mohamed, et al. Computational drug discovery and repurposing for the treatment of COVID-19: A systematic review

[2] Min Jiang, et al. Genotypic and phenotypic analyses of hepatitis C virus variants observed in clinical studies of VX-222, a nonnucleoside NS5B polymerase inhibitor

[3] Adrian M Di Bisceglie, et al. VX-222, a non-nucleoside NS5B polymerase inhibitor, in telaprevir-based regimens for genotype 1 hepatitis C virus infection

[4] Weiwei Xue, et al. Molecular modeling and residue interaction network studies on the mechanism of binding and resistance of the HCV NS5B polymerase mutants to VX-222 and ANA598

[5] Guanghui Yi, et al. Biochemical study of the comparative inhibition of hepatitis C virus RNA polymerase by VX-222 and filibuvir

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Keywords: VX-222, VCH-222, Lomibuvir supplier, HCV Protease, inhibitors, activators


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