TMC647055, a Potent Nonnucleoside Hepatitis C Virus NS5B Polymerase Inhibitor with Cross-Genotypic Coverage

被引：32

作者：

Devogelaere, Benoit ^{[1
]}

Berke, Jan Martin ^{[1
]}

Vijgen, Leen ^{[1
]}

Dehertogh, Pascale ^{[1
]}

Fransen, Els ^{[1
]}

Cleiren, Erna ^{[1
]}

van der Helm, Liesbet ^{[1
]}

Nyanguile, Origene ^{[1
]}

Tahri, Abdellah ^{[1
]}

Amssoms, Katie ^{[1
]}

Lenz, Oliver ^{[1
]}

Cummings, Maxwell D. ^{[2
]}

Clayton, Reginald F. ^{[1
]}

Vendeville, Sandrine ^{[1
]}

Raboisson, Pierre ^{[1
]}

Simmen, Kenneth A. ^{[1
]}

Fanning, Gregory C. ^{[1
]}

Lin, Tse-I ^{[1
]}

机构：

[1] Janssen Infect Dis, Beerse, Belgium

[2] Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2012年 / 56卷 / 09期

关键词：

DEPENDENT RNA-POLYMERASE; ANTIVIRAL ACTIVITY; REPLICATION; DISCOVERY; IDENTIFICATION; OPTIMIZATION; BOCEPREVIR; TELAPREVIR; MECHANISM; PROFILE;

D O I：

10.1128/AAC.00245-12

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

Hepatitis C virus (HCV) infection is a major global health burden and is associated with an increased risk of liver cirrhosis and hepatocellular carcinoma. There remains an unmet medical need for efficacious and safe direct antivirals with complementary modes of action for combination in treatment regimens to deliver a high cure rate with a short duration of treatment for HCV patients. Here we report the in vitro inhibitory activity, mode of action, binding kinetics, and resistance profile of TMC647055, a novel and potent nonnucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase. In vitro combination studies with an HCV NS3/4A protease inhibitor demonstrated potent suppression of HCV RNA replication, confirming the potential for combination of these two classes in the treatment of chronic HCV infection. TMC647055 is a potent nonnucleoside NS5B polymerase inhibitor of HCV replication with a promising in vitro biochemical, kinetic, and virological profile that is currently undergoing clinical evaluation.

引用

页码：4676 / 4684

页数：9

共 46 条

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