[HCV: small molecule NS3 protease inhibitors -- Boehringer Ingelheim -- BILN 2061]
>>Nature AOP, published online 26 October 2003; doi:10.1038/nature02099
An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus
DANIEL LAMARRE1, PAUL C. ANDERSON2, MURRAY BAILEY2, PIERRE BEAULIEU2, GORDON BOLGER1, PIERRE BONNEAU1, MICHAEL BÖS2, DALE R. CAMERON2,*, MIREILLE CARTIER1, MICHAEL G. CORDINGLEY1, ANNE-MARIE FAUCHER2, NATHALIE GOUDREAU2, STEPHEN H. KAWAI2, GEORGE KUKOLJ1, LISETTE LAGACÉ1, STEVEN R. LAPLANTE2, HANS NARJES3, MARC-ANDRÉ POUPART2, JEAN RANCOURT2, ROEL E. SENTJENS4, ROGER ST GEORGE5, BRUNO SIMONEAU2, GERHARD STEINMANN3, DIANE THIBEAULT1, YOULA S. TSANTRIZOS2, STEVEN M. WELDON5, CHAN-LOI YONG5 & MONTSE LLINÀS-BRUNET2
1 Departments of Biological Sciences Boehringer Ingelheim (Canada) Ltd, Laval, Québec, H7S 2G5, Canada
2 Chemistry, Research and Development, Boehringer Ingelheim (Canada) Ltd, Laval, Québec, H7S 2G5, Canada
3 Clinical Research, Boehringer Ingelheim Pharma KG, Biberach 88397, Germany
4 Academisch Medisch Center, 1105 AZ, Amsterdam, The Netherlands
5 Research and Development, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877-0368, USA
* Present address: Micrologix Biotech Inc., BC Research Complex, 3650 Wesbrook Mall, Vancouver, British Columbia, V6S 2L2, Canada
Correspondence and requests for materials should be addressed to D.L. (dlamarre@lav.boehringer-ingelheim.com).
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.<<
This would appear to be preliminary results of a PI.
Cheers, Tuck |
