Size | Price | Stock | Qty |
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1mg |
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5mg |
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10mg |
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50mg |
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100mg |
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Other Sizes |
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ln Vitro |
Lomibuvir (VX-222) suppresses the WT HCV 1b/Con1 replicon at a 5.2 nM EC50. Lomibuvir inhibits the mutant replicons M423T, L419M, and I482L, having EC50 values of 79.8, 563.1, and 45.3 nM, in that order. Lomibuvir exhibits a significant suppression of primer extension while also marginally reducing de novo initiation. For primer-extended RNA synthesis, lomibuvir's IC50 is 31 nM[1]. Lomibuvir is an allosteric inhibitor of the NS5B polymerase of the hepatitis C virus that is non-nucleoside[2].
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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. It is anticipated that VCH-222 is actively transported in the liver and excreted mostly intact in bile or as glucuronide adducts after undergoing biotransformation by multiple enzymes (CYP1A1, 2A6, 2B6, 2C8, CYP 3A4, UGT1A3).[3]
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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 |
At a density of 4 × 104 cells/well, trypsinized Huh7.5 cells containing HCV RNA replicons are plated into 48-well plates. Next day, 200 μL of full medium is added to VX-222, and the medium is changed again. Real-time reverse transcription-PCR (RT-PCR) is used to quantify viral RNAs after 48 hours of total RNA extraction. Nonlinear regression analysis using log curve fitting is used to determine the effective drug concentrations (EC50) that reduced HCV RNA replicon levels by 50%.
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Animal Protocol |
Rats or dogs
5 mg/kg for rats or 10 mg/kg for dogs By oral gavage |
References |
[1]. Yi G, Deval J, et al. Biochemical study of the comparative inhibition of hepatitis C virus RNA polymerase by VX-222 and filibuvir. Antimicrob Agents Chemother. 2012;56(2):830-837.
[2]. Li P, Dorsch W, et al. Discovery of Novel Allosteric HCV NS5B Inhibitors. 2. Lactam-Containing Thiophene Carboxylates. ACS Med Chem Lett. 2017;8(2):251-255. Published 2017 Jan 31. [3]. M. Rodriguez-Torres et al. SAFETY AND ANTIVIRAL ACTIVITY OF THE HCV NON-NUCLEOSIDE POLYMERASE INHIBITOR VX-222 IN TREATMENT-NAIVE GENOTYPE 1 HCV-INFECTED PATIENTS Journal of Hepatology Volume 52, Supplement 1 , Page S14, April 2010 |
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 # |
1026785-55-6
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Related CAS # |
cis-Lomibuvir;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 |
VX-222; VX222; VCH-222; VCH222; VX 222; VCH 222; Lomibuvir; VX-22; VX22; VX 22
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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) |
DMSO : 89~100 mg/mL (199.7~224.4 mM)
Ethanol : ~89 mg/mL (~199.7 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.61 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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 |
Structures of filibuvir and VX-222 (A) and the locations of three resistance mutations in the thumb II domain targeting the thumb allosteric binding site (B). Antimicrob Agents Chemother . 2012 Feb;56(2):830-7. td> |
Effects of filibuvir, VX-222, and ANA-598 on the EC50s of HCV replicons. Antimicrob Agents Chemother . 2012 Feb;56(2):830-7. td> |
Examination of filibuvir or VX-222 binding based on DSF spectroscopy. Antimicrob Agents Chemother . 2012 Feb;56(2):830-7. td> |
Binding affinities and kinetics for filibuvir and VX-222 by SPR. Antimicrob Agents Chemother . 2012 Feb;56(2):830-7. td> |