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- Title
An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus.
- Authors
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; Sentjens, Roel E.
- 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.
- Subjects
HEPATITIS C virus; LIVER diseases; ANTIVIRAL agents; PROTEASE inhibitors; DRUG development
- Publication
Nature, 2003, Vol 426, Issue 6963, p186
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature02099