| Description | Lomibuvir (VCH-222) is a selective, non-nucleoside allosteric inhibitor of HCV NS5B polymerase (RdRp) with a Kd of 17 nM. Lomibuvir inhibits the 1b/Con1 HCV subgenomic replicon with an EC 50 of 5.2 nM. Lomibuvir preferentially inhibits elongative RNA synthesis rather than de novo -initiated RNA synthesis [1]. |
| In vitro | Lomibuvir (VX-222) 以EC50为5.2 nM的效力抑制WT HCV 1b/Con1复制子。对于突变复制子M423T、L419M和I482L，Lomibuvir的EC50分别为79.8 nM、563.1 nM和45.3 nM。Lomibuvir轻微减少了de novo启动，但强烈抑制引物延伸。Lomibuvir对引物延伸的RNA合成的IC50为31 nM [1]。Lomibuvir是一种非核苷类、与位点异源的丙型肝炎病毒NS5B聚合酶抑制剂，已证明其在临床上有效 [2]。 |
| In vivo | 在大鼠和犬类动物中，Lomibuvir展示了良好的药代动力学特性，包括低总体清除率和优异的口服生物利用度（高于30%）以及良好的ADME特性。Lomibuvir经由数个酶（CYP1A1、2A6、2B6、2C8、CYP3A4、UGT1A3）生物转化，预计在肝脏中主动转运，并主要以完整形式或作为糖苷结合物通过胆汁排泄。[3] |
| Cell experiments | 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 quanti?ed 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 ?tting.(Only for Reference) |
| Target activity | HCV NS5B 1a:0.94-1.2 μM |
| Synonyms | VX-222, VCH-222 |
| molecular weight | 445.61 |
| Molecular formula | C25H35NO4S |
| CAS | 1026785-55-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: 82 mg/mL (184 mM) DMSO: 82 mg/mL (184 mM) |
| References | 1. Bedard J, et al. J Hepatol, 2009, 50(Suppl 1), S340. 2. Yi G, et al. Antimicrob Agents Chemother, 2012, 56(2), 830-837. 3. Chauret N, et al. J Hepatol, 2009, 50(Suppl 1), S341-S342. |