"目录号: HY-14775
Anti-infection-
Nesbuvir 是一种非核苷抑制剂，抑制丙型肝炎病毒(HCV) 非结构蛋白 5B (NS5B) 聚合酶。
HCV
相关产品
Asunaprevir-PSI-7977-Simeprevir-Daclatasvir-Paritaprevir-Telaprevir-Boceprevir-Ledipasvir-Ombitasvir-MK-5172-Elbasvir-ABT-333-Ribavirin-R-1479-Balapiravir-
生物活性
Description
Nesbuvir is a nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) polymerase.
IC50& Target
EC50: 9 nM (NS3V170A), 13 nM (NS3V170A), 15 nM (NS3K583T), 13 nM (NS5BI424V)[1]
In Vitro
Replicon cells are treated with 1 mg/mL G418 and combinations of the two compounds. Nesbuvir (HCV-796) is added to 40 or 80 nM (approximately 10 and 20 times the EC50in a 3-day replicon inhibition assay, respectively) and Boceprevir is added to 400 or 800 nM (approximately 2 and 4 times the EC50, respectively). The EC50s for Nesbuvir and Boceprevir for the parental replicon in the transient expression assay are comparable to those obtained in the 3-day inhibition assay with the stable replicon cells; the EC50for Nesbuvir in the transient expression assay is 14 nM, whereas it is 5 nM for the stable replicon; and the EC50for Boceprevir in the transient expression assay is 608 nM, whereas it is 201 nM for the stable replicon[1].
In Vivo
Among a huge variety of yet characterized nucleoside and non-nucleoside inhibitors (NNI), the benzofurane derivative NNI Nesbuvir (HCV-796) is demonstrated to yield significant antiviral effects in mice with chimeric human livers and in patients infected with HCV. HCV-796 binds to a hydrophobic binding pocket at the “palm” domain of NS5B; however, its mode of inhibition remains to be defined[2].
Clinical Trial
NCT00367887
Wyeth is now a wholly owned subsidiary of Pfizer-ViroPharma
Hepatitis C
October 2006
Phase 2
NCT00407173
Wyeth is now a wholly owned subsidiary of Pfizer-ViroPharma
Healthy
November 2006
Phase 1
NCT00314054
Wyeth is now a wholly owned subsidiary of Pfizer-ViroPharma
Hepatitis C-Hepatic Insufficiency
May 2006
Phase 1
NCT00500721
Wyeth is now a wholly owned subsidiary of Pfizer-ViroPharma
Healthy
June 2007
Phase 1
NCT00410254
Wyeth is now a wholly owned subsidiary of Pfizer
Healthy
June 2007
Phase 1
NCT00385190
Wyeth is now a wholly owned subsidiary of Pfizer
Healthy
July 2006
Phase 1
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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 Feb;53(2):401-11.
[2].Reich S, et al. Mechanisms of activity and inhibition of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem. 2010 Apr 30;285(18):13685-93.