Development of boceprevir: A first-in-class direct antiviral treatment for chronic hepatitis C infection

Annals of the New York Academy of Sciences

Volumn 1291, Issue 1, 2013, Pages 69-76

  Hazuda, Daria J ^a   Burroughs, Margaret ^a   Howe, Anita Y M ^a   Wahl, Janice ^a   Venkatraman, Srikanth ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Hepatitis C virus; Ketoamide; NS3 4A protease inhibitor

Indexed keywords

BOCEPREVIR;

ANTIVIRAL ACTIVITY; ANTIVIRAL THERAPY; ARTICLE; CHEMICAL PHENOMENA; DRUG MECHANISM; DRUG RESPONSE; DRUG SOLUBILITY; DRUG STRUCTURE; ENZYME INHIBITION; HEPATITIS C; LONG TERM CARE; MOLECULAR WEIGHT; NONHUMAN; PREDICTION; VIRUS INHIBITION; VIRUS REPLICATION;

EID: 84880418320     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/nyas.12218     Document Type: Article

References (31)

1. McHutchison, J.G. & B.R. Bacon. 2005. Chronic hepatitis C: an age wave of disease burden. Am. J. Manag. Care 11(10 Suppl.): S286-S295.
2. Manns, M.P., G Foster, J.K. Rockstroh, et al. 2007. The way forward in HCV treatment-finding the right path. Nat. Rev. Drug Discovery 6: 991-1000.
3. Centers for Disease Control and Prevention. Division of Viral Hepatitis and National Center for HIV/AIDS. 2012. Viral Hepatitis, STD, and TB Prevention. Aug 16, 2012. Accessed October 26, 2012. http://www.cdc.gov/hepatitis/c/cfaq.htm.
4. Susser, S., C. Welch, Y. Wang, et al. 2009. Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. Hepatology 50: 1709-1718.
5. Webster, D.P., P. Klenerman, J. Collier, et al. 2009. Development of novel treatments for hepatitis C. Lancet Infect. Dis. 9: 108-117.
6. Zein, N.N., J. Rakela, E.L. Krawitt, et al. 1996. Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy. Ann. Intern. Med. 125: 634-639.
7. Ciesek, S. & M.P. Manns. 2011. The dawn of a new era in HCV therapy. Nat. Rev. Gastroenterol. Hepatol. 8: 69-71.
8. Kim, J.L., K.A. Morgenstern, C. Lin, et al. 1996. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87: 343-355.
9. Yao, N., P. Reichert, S.S. Taremi, et al. 1999. Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase. Structure 7: 1353-1363.
10. Steinkuhler, C., A. Urbani, L. Tomei, et al. 1996. Activity of purified hepatitis C virus protease NS3 on peptide substrates. J. Virol. 70: 6694-6700.
11. Sali, D.L., R. Ingram, M. Wendel, et al. 1998. Serine protease of hepatitis C virus expressed in insect cells as the NS3/4A complex. Biochemistry 37: 3392-3401.
12. Shoji, I., T. Suzuki, S. Chieda, et al. 1995. Proteolytic activity of NS3 serine proteinase of hepatitis C virus efficiently expressed in Escherichia coli. Hepatology 22: 1648-1655.
13. Taremi, S.S., B. Beyer, M. Maher, et al. 1998. Construction, expression, and characterization of a novel fully activated recombinant single-chain hepatitis C virus protease. Protein Sci. 7: 2143-2149.
14. Zhang, R., B.M. Beyer, J. Durkin, et al. 1999. A continuous spectrophotometric assay for the hepatitis C virus serine protease. Anal. Biochem. 270: 268-275.
15. Bogen, S.L., A. Arasappan, F. Bennett, et al. 2006. Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication. J. Med. Chem. 49: 2750-2757.
16. Chen, K.X., F.G. Njoroge, A. Arasappan, et al. 2006. Novel potent hepatitis C virus NS3 serine protease inhibitors derived from proline-based macrocycle. J. Med. Chem. 49: 995-1005.
17. Venkatraman, S., V. Velazzquez, W. Wu, et al. 2009. Discovery and structure-activity relationship of P1-P3 ketoamide derived macrocyclic inhibitors of hepatitis C virus NS3 protease. J. Med. Chem. 52: 336.
18. Venkatraman, S., S.L. Bogen, A. Arasappan, et al. 2006. Discovery of (1R, 5 S)-N-[3-amino-1-(cyclobutylmethyl)-2-3-dioxopropyl]-3-[2(S)-[[[(1, 1-dimethylethyl)-amino]carbonyl]amio]-3, 3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable, hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection. J. Med. Chem. 49: 6074-6086.
19. Prongay, A.J., Z. Guo, N. Yao, et al. 2008. Discovery of the HCV NS3/4A protease inhibitor (1R, 5S)-N-[3-amino-1-(cyclobutylmethyl)-2, 3-dioxopropyl]-3-[2(S)-[[[(1, 1-dimethylethyl)amino]carbonyl]amino]-3, 3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II. Key steps in structure-based optimization. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Acc. Chem. Res. 41: 50-59.
20. Njorge, F.G., K.X. Chen, N.Y. Shih & J.J. Piwinski. 2008. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Acc. Chem. Res. 41: 50-59.
21. Foy, E., K. Li, R. Sumpter, Jr., et al. 2005. Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling. Proc. Natl. Acad. Sci. U. S. A. 102: 2986-2991.
22. Jensen, D., T. Morgan, P. Marcellin, et al. 2006. Rapid virologic response at week 4 (RVR) of peginterferon alfa 2a (40kD) plus ribavirin treatment predicts sustained virological response (SVR) after 24 weeks in genotype 1 patients. Hepatology 43: 954-960.
23. Mangia, A, N. Minerva, D. Bacca, et al. 2008. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. Hepatology 47: 43-50.
24. Nagaki, M., M. Shimizu, J.I. Sugihara, et al. 2009. Clinical trial: extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late responders. Aliment Pharmacol. Ther. 30: 343-351.
25. Bacon, B.R., S.C. Gordon, E. Lawitz, et al. 2011. Boceprevir for previously treated chronic HCV genotype 1 infection. N. Engl. J. Med. 364: 1207-1217.
26. Poordad, F., McCone, B.R. Baco, et al. 2011. Boceprevir for untreated chronic HCV genotype 1 infection. N. Engl. J. Med. 364: 1195-1206.
27. Birnkrant, D. Presented at: U.S. Food and Drug Administration Antiviral Drugs Advisory Committee Meeting; April 27-28, 2011. Silver Spring, MD.
28. Neumann, A.U, N.P. Lam, H. Dahari, et al. 1998. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282: 103-107.
29. Cuevas, J.M., F. González-Candelas, A. Moya & R. Sanjuán. 2009. Effect of ribavirin on the mutation rate and spectrum of hepatitis C virus in vivo. J. Virol. 83: 5760-5764.
30. Rong, L., H. Dahari, R.M. Ribeiro & A.S. Perelson. 2010. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci. Transl. Med. 2: 1-9.
31. Howe, A.Y.M., J. Long, R. Barnard, et al. 2012. Durability of response and analysis of resistance associated variants during long term follow up with boceprevir/peginterferon/ribavirin: an interim analysis. Hepatology 56: 712A.