1. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus.
- Author
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Lamarre, Daniel, Anderson, Paul C., Bailey, Murray, Beaulieu, Pierre, Bolger, Gordon, Bonneau, Pierre, Bös, Michael, Cameron, Dale R., Cartier, Mireille, Cordingley, Michael G., Faucher, Anne-Marie, Goudreau, Nathalie, Kawai, Stephen H., Kukolj, George, Lagacé, Lisette, LaPlante, Steven R., Narjes, Hans, Poupart, Marc-André, Rancourt, Jean, and Sentjens, Roel E.
- Subjects
HEPATITIS C virus ,LIVER diseases ,ANTIVIRAL agents ,PROTEASE inhibitors ,DRUG development - Abstract
Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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