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1mg |
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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Purity: ≥98%
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 that targets the NS5B RNA-dependent RNA polymerase of the hepatitis C virus (HCV), with IC50 values ranging from 0.94 to 1.2 μM. For the treatment of chronic HCV and chronic HCV infections, it has been studied in clinical trials. In patients with genotype 1 HCV infection who were chronically infected, VX-222 showed significant reductions in plasma HCV RNA in phase 1 and 2 clinical trials, indicating effective antiviral efficacy.
Targets |
HCV NS5B 1a (IC50 = 0.94 μM); HCV NS5B 1b (IC50 = 1.2 μM)
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ln Vitro |
VX-222 attaches itself to the HCV RNA-dependent RNA polymerase's thumb II allosteric pocket. With an IC50 of 0.94 and 1.2 μM, respectively, VX-222 shows non-competitive and selective inhibition in HCV NS5B of genotypes 1a and 1b. Subgenomic HCV genotypes 1a and 1b are specifically inhibited by VX-222, with EC50 values of 22.3 and 11.2 nM, respectively. (Source: ) Similarly, VX-222 inhibits the 1b/Con1 HCV subgenomic replicon with an EC50 of 5 nM, according to a recent study. While having little to no effect on de novo-initiated RNA synthesis, VX-222 preferentially inhibits primer-dependent RNA synthesis.
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ln Vivo |
VCH-222 exhibits fine pharmacokinetic properties in rats and dogs, such as low total body clearance, excellent oral bioavailability (more than 30%), and good ADME characteristics. Multiple enzymes (CYP1A1, 2A6, 2B6, 2C8, CYP 3A4, UGT1A3) biotransform VCH-222. It is expected that VCH-222 is actively transported in the liver and excreted mostly intact in bile or as glucuronide adducts.
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Enzyme Assay |
VX-222's inhibitory effect on HCV NS5B activity is quantified by measuring the amount of radiolabeled UTP incorporated by the enzyme's C-terminal ∆21 truncated version in a freshly synthesized RNA using a homopolymeric RNA template / primer called poly rA / oligo dT. Liquid scintillation counters are used to quantitatively detect incorporated radioactivity. In vitro kinetics of VX-222-induced inhibition of HCV NS5B from genotype 1b strain BK are ascertained by employing the C-terminal ∆21 truncated form of NS5B. When VX-222 (1 to 1.5 μM) is combined with 0.89 to 6.70 μCi of [α-33P]-labeled UTP and 10 to 75 μM nonradioactive UTP, testing is conducted. 18 minutes at 22 °C are given to RNA-dependent RNA polymerase reactions.
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Cell Assay |
Trypsinized Huh7.5 cells containing HCV RNA replicons are plated at a density of 4 × 104 cells per well into 48-well plates. The following day, 200 μL of the full medium is added to the new medium along with VX-222. Following a 48-hour period, total RNA is extracted, and real-time reverse transcription-PCR (RT-PCR) is used to quantify viral RNAs. With the use of nonlinear regression analysis and log curve fitting, the effective drug concentrations (EC50) that decreased HCV RNA replicon levels by 50% are determined.
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Animal Protocol |
Rats or dogs
5 mg/kg for rats or 10 mg/kg for dogs By oral gavage |
References |
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Molecular Formula |
C25H35NO4S
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Molecular Weight |
445.61
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Exact Mass |
445.23
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Elemental Analysis |
C, 67.38; H, 7.92; N, 3.14; O, 14.36; S, 7.19
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CAS # |
1026785-59-0
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Appearance |
Solid powder
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SMILES |
CC1CCC(CC1)C(=O)N(C2CCC(CC2)O)C3=C(SC(=C3)C#CC(C)(C)C)C(=O)O
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InChi Key |
WPMJNLCLKAKMLA-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C25H35NO4S/c1-16-5-7-17(8-6-16)23(28)26(18-9-11-19(27)12-10-18)21-15-20(13-14-25(2,3)4)31-22(21)24(29)30/h15-19,27H,5-12H2,1-4H3,(H,29,30)
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Chemical Name |
5-(3,3-dimethylbut-1-ynyl)-3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid
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Synonyms |
TD-4208; TD4208; GSK-1160724; GSK-1160724; TD 4208; GSK1160724; trade name: Yupelri; TD-4208; GSK 1160724
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2441 mL | 11.2206 mL | 22.4411 mL | |
5 mM | 0.4488 mL | 2.2441 mL | 4.4882 mL | |
10 mM | 0.2244 mL | 1.1221 mL | 2.2441 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00958152 | Completed | Drug: VCH-222 Drug: telaprevir |
Hepatitis C | Vertex Pharmaceuticals Incorporated |
May 15, 2021 | Phase 1 |
NCT01581138 | Completed | Drug: VX-222 Drug: telaprevir |
Chronic Hepatitis C Virus | Vertex Pharmaceuticals Incorporated |
July 2012 | Phase 2 |
NCT01516918 | Completed | Drug: VX-222 Drug: telaprevir |
Chronic Hepatitis C Virus | Vertex Pharmaceuticals Incorporated |
February 2012 | Phase 2 |
NCT00911963 | Completed | Drug: VCH-222 Drug: ribavirin |
Hepatitis C | Vertex Pharmaceuticals Incorporated |
January 12, 2018 | Phase 1 Phase 2 |
NCT01581138 | Completed | Drug: VX-222 Drug: telaprevir |
Chronic Hepatitis C Virus | Vertex Pharmaceuticals Incorporated |
July 2012 | Phase 2 |