"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.