| Description | Nesbuvir is a selective hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent polymerase inhibitor.Nesbuvir has an IC50 of 9 nM against hepatocellular carcinoma cells containing 1b HCV replicons. |
| In vitro | Nesbuvir (40 or 80 nM) (approximately 10 and 20 times the EC50 in a 3-day replicon inhibition assay, respectively). The EC50 for Nesbuvir in the transient expression assay is 14 nM, whereas it is 5 nM for the stable replicon.[1]Nesbuvir (0.1 and 1 μM; Huh-7 cells; for 16 days) reduced about 3.6 log10 and 4.2 log10 HCV RNA levels, respectively.[3] |
| In vivo | Nesbuvir is demonstrated to yield significant antiviral effects in mice with chimeric human livers and in patients infected with HCV.[2] Nesbuvir (chimeric mouse model) treatment resulted in a 2.02 +/- 0.55 log reduction in HCV titer, whereas in combination with interferon using a suboptimal dose of 30 mg/kg three times per day showed a 2.44 log reduction and were better than interferon treatment only.[5] |
| Cell experiments | Huh7-BB7 cells are seeded at a density of 20,000 cells per 100 mm dish in DMEM supplemented with 2% FBS, 1 mg/mL G418, and various concentrations of Nesbuvir and/or Boceprevir with DMSO at a final concentration of 0.5% (vol/vol). The medium is removed and is replaced with a fresh medium with the appropriate compound concentrations every 3 or 4 days. After 7 days, the cells are split 1 to 10, placed into fresh 100 mm dishes, and incubated with medium with the appropriate compound concentrations. After 20 days, the medium is removed and the cells are fixed with 7% (wt/vol) formaldehyde and stained with 1% (wt/vol) crystal violet in 50% (vol/vol) ethanol [1]. |
| Target activity | NS3V170A:13 nM (EC50), NS3V170A:9 nM (EC50), NS5BI424V:13 nM (EC50), NS3K583T:15 nM (EC50), NS5B:5 nM |
| Synonyms | HCV-796 |
| molecular weight | 446.49 |
| Molecular formula | C22H23FN2O5S |
| CAS | 691852-58-1 |
| Storage | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 45.0 mg/mL (100.8 mM) |
| References | 1. Flint M, et al. Selection and characterization of hepatitis C virus replicons dually resistant to the polymerase and protease inhibitors HCV-796 and boceprevir (SCH 503034). Antimicrob Agents Chemother. 2009;53(2):401-411. 2. Reich S, et al. Mechanisms of activity and inhibition of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem. 2010;285(18):13685-13693. 3. Howe AY, et al. Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796. Antimicrob Agents Chemother. 2008;52(9):3327-3338. 4. Meshram RJ, et al. Effective epitope identification employing phylogenetic, mutational variability, sequence entropy, and correlated mutation analysis targeting NS5B protein of hepatitis C virus: from bioinformatics to therapeutics. J Mol Recognit. 2015;28(8):492-505. 5. Kneteman NM, et al. HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti-hepatitis C virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology. 2009;49(3):745-752. |