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    Lomibuvir (VX 222; VCH 222)
    Lomibuvir (VX 222; VCH 222)

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    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V0726
    CAS #: 1026785-59-0 or 1026785-55-6 Purity ≥98%

    Description: Lomibuvir (also known as Lomibuvir (also called VX-22; S-1480; VCH222; VX22; S1480; VX222; VCH-222; VX-222) is a novel, potent and selective non-nucleoside inhibitor/NNI of hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase with IC50s in the range of 0.94-1.2 μM. It has been investigatedin clinical trials for the treatment of chronic HCV and chronic HCV infections. ) is a novel, potent and selective non-nucleoside inhibitor/NNI of hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase with IC50s of 0.94-1.2 μM, it has been investigatedin clinical trials for the treatment of chronic HCV and chronic HCV infections. 

    References: Antimicrob Agents Chemother. 2012 Feb;56(2):830-7; J Hepatol, 2009, 50(Suppl 1), S341-S342.

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    Molecular Weight (MW)445.61
    CAS No.1026785-59-0 or 1026785-55-6 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 89 mg/mL (199.7 mM)
    Water: <1 mg/mL
    Ethanol: <89 mg/mL (199.7 mM)
    Solubility (In vivo)30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL
    SynonymsLomibuvir; VX222; VX-222; VX 22; VCH 222; VX22; S-1480; S1480; S 1480; VX 222; VCH-222; VCH222; VX-22;

    Chemical Name: 5-(3,3-dimethylbut-1-yn-1-yl)-3-((1r,4R)-N-((1r,4R)-4-hydroxycyclohexyl)-4-methylcyclohexane-1-carboxamido)thiophene-2-carboxylic acid

    SMILES Code: O=C(C1=C(N([[email protected]]2CC[[email protected]](O)CC2)C([[email protected]]3CC[[email protected]](C)CC3)=O)C=C(C#CC(C)(C)C)S1)O

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    In Vitro

    In vitro activity: VX-222 binds to the thumb II allosteric pocket of the HCV RNA-dependent RNA polymerase. VX-222 exhibits non-competitive and selective inhibition in HCV NS5B of genotype 1a and 1b, with IC50 of 0.94 and 1.2 μM, respectively. VX-222 selectively inhibits the replication of subgenomic HCV genotype 1a and 1b with an EC50 of 22.3 and 11.2 nM, respectively. Similarly, a recent study shows that VX-222 inhibits the 1b/Con1 HCV subgenomic replicon, with an EC50 of 5 nM. VX-222 preferentially inhibits primer-dependent RNA synthesis, showing only a modest or no effect on de novo-initiated RNA synthesis.

    Kinase Assay: The inhibitory effect of VX-222 on HCV NS5B activity is measured by evaluating the amount of radiolabeled UTP incorporated by the C-terminal ∆21 truncated version of enzyme in a newly synthesized RNA using a homopolymeric RNA template / primer namely poly rA / oligo dT. Quantitative detection of incorporated radioactivity is done using a liquid scintillation counter. The in vitro kinetics of inhibition of HCV NS5B from genotype 1b strain BK by VX-222 are determined using the C-terminal ∆21 truncated version of NS5B. VX-222 (1 to 1.5 μM) is tested in the presence of 10 to 75 μM nonradioactive UTP mixed with 0.89 to 6.70 μCi of [α-33P]-labeled UTP. RNA-dependent-RNA polymerase reactions are allowed to proceed for 18 min at 22 °C.

    Cell Assay: Huh7.5 cells harboring HCV RNA replicons are trypsinized and plated into 48-well plates at a concentration of 4 × 104 cells/well. The next day the medium is changed and VX-222 is added in 200 μL of complete medium. After 48 hours, 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.

    In VivoIn rats and dogs, VCH-222 displays fine pharmacokinetic profile, including low total body clearance and excellent oral bioavailability (greater than 30%) and good ADME properties. VCH-222 is biotransformed by several enzymes (CYP1A1, 2A6, 2B6, 2C8, CYP 3A4, UGT1A3) and is predicted to be actively transported in liver and excreted mainly intact in bile or as glucuronide adducts.
    Animal modelRats or dogs
    Formulation & DosageFormulated in 30% PEG; 5 mg/kg for rats or 10 mg/kg for dogs; P.O. 

    Antimicrob Agents Chemother. 2012 Feb;56(2):830-7; J Hepatol, 2009, 50(Suppl 1), S341-S342.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    VX-222 (VCH-222, Lomibuvir)

    Effects of filibuvir, VX-222, and ANA-598 on the EC50s of HCV replicons. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7.

    VX-222 (VCH-222, Lomibuvir)

    Examination of RNA synthesis by mutant HCV RdRps. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7.


    VX-222 (VCH-222, Lomibuvir)

    Effects of nonnucleoside analog inhibitors on RNA synthesis by the recombinant HCV RdRp. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7.

    VX-222 (VCH-222, Lomibuvir)

    Examination of filibuvir or VX-222 binding based on DSF spectroscopy. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7. 

    VX-222 (VCH-222, Lomibuvir)

    Binding affinities and kinetics for filibuvir and VX-222 by SPR. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7. 

    VX-222 (VCH-222, Lomibuvir)

    Competition binding experiments. Antimicrob Agents Chemother. 2012 Feb;56(2):830-7. 



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