Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect

Min Gao, Richard E. Nettles, Makonen Belema, Lawrence B. Snyder, Nguyen Van N., Robert A. Fridell, Michael H. Serrano-Wu, David R. Langley, Jin-Hua Sun, Donald R. O’Boyle, Julie A. Lemm, Chunfu Wang, Jay O. Knipe, Caly Chien, Richard J. Colonno, Dennis M. Grasela, Nicholas A. Meanwell () and Lawrence G. Hamann
Additional contact information
Min Gao: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Richard E. Nettles: Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
Makonen Belema: Department of Discovery Chemistry,
Lawrence B. Snyder: Department of Discovery Chemistry,
Nguyen Van N.: Department of Discovery Chemistry,
Robert A. Fridell: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Michael H. Serrano-Wu: Department of Discovery Chemistry,
David R. Langley: Department of Computer-Aided Drug Design,
Jin-Hua Sun: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Donald R. O’Boyle: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Julie A. Lemm: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Chunfu Wang: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Jay O. Knipe: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Caly Chien: Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
Richard J. Colonno: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Dennis M. Grasela: Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
Nicholas A. Meanwell: Department of Discovery Chemistry,
Lawrence G. Hamann: Department of Discovery Chemistry,

Nature, 2010, vol. 465, issue 7294, 96-100

Abstract: New drugs for hepatitis C The development of direct-acting antiviral agents to treat chronic hepatitis C virus (HCV) infection, much needed clinically, has focused largely on inhibitors of two viral enzymes, the protease NS3 and NS5B, an RNA-dependent RNA polymerase essential for HCV replication. BMS-790052, identified using chemical genetics as a powerful specific HCV inhibitor, is a small-molecule inhibitor of a third viral molecule that has no known enzyme activity, the non-structural protein 5A (NS5A). A research team from Bristol-Myers Squibb this week reports on the discovery and virological profile of BMS-790052 and discloses clinical trial observations with this compound in normal healthy volunteers and HCV-infected subjects. These results establish proof-of-concept for HCV NS5A inhibition as a clinically relevant mechanism. In vitro data point to synergistic interactions with known HCV inhibitors, suggesting that cocktails of antiviral agents may be a viable therapeutic approach.

Date: 2010
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature08960 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:465:y:2010:i:7294:d:10.1038_nature08960

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature08960

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().