Boceprevir, an NS3 Protease Inhibitor of HCV

被引:47
作者
Berman, Kenneth [1 ]
Kwo, Paul Y. [1 ]
机构
[1] Indiana Univ, Dept Med, Div Gastroenterol Hepatol, Sch Med, Indianapolis, IN 46202 USA
关键词
HCV; Interferon; Ribovirin; Protease; Resistance; Hepatitis C; Stat-C; HEPATITIS-C-VIRUS; ALPHA-2B PLUS RIBAVIRIN; COMBINATION THERAPY; RESISTANCE MUTATIONS; NULL RESPONDERS; PEGINTERFERON; INTERFERON; GENOTYPE-1; IDENTIFICATION; SCH-503034;
D O I
10.1016/j.cld.2009.05.008
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Hepatitis C virus (HCV) is a major cause of chronic liver disease leading to death from liver failure or hepatocellular carcinoma. Hepatitis C is the most common indication for liver transplantation worldwide and is a major cause of the increased incidence of hepatocellular cancer in the United States. The current paradigm for HCV treatment relies on pegylated interferon and ribavirin as agents that enhance endogenous mechanisms for viral clearance and are dependent on host factors. In patients with genotype 1 HCV infection, sustained viral response (SVR) rates remain suboptimal, with less than half of genotype 1-infected individuals going on to achieve SVR. This has led to a shift in the investigational focus for treatment of HCV toward specifically targeted antiviral therapy for HCV agents. This review focuses on boceprevir, a protease inhibitor, and discusses its mechanism of action, effects on HCV, and viral resistance.
引用
收藏
页码:429 / +
页数:13
相关论文
共 29 条
  • [1] Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3•4A protease inhibitors in treatment-naive subjects
    Bartels, Doug J.
    Zhou, Yi
    Zhang, Eileen Z.
    Marcial, Michelle
    Byrn, Randal A.
    Pfeiffer, Thomas
    Tigges, Ann M.
    Adiwijaya, Bambang S.
    Lin, Chao
    Kwong, Ann D.
    Kieffer, Tara L.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2008, 198 (06): : 800 - 807
  • [2] Hepatitis C virus replicons: potential role for drug development
    Bartenschlager, R
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (11) : 911 - 916
  • [3] Extended treatment duration for hepatitis C virus type 1: Comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin
    Berg, T
    von Wagner, M
    Nasser, S
    Sarrazin, C
    Heintges, T
    Gerlach, T
    Buggisch, P
    Goeser, T
    Rasenack, J
    Pape, GR
    Schmidt, WE
    Kallinowski, B
    Klinker, H
    Spengler, U
    Martus, P
    Alshuth, U
    Zeuzem, S
    [J]. GASTROENTEROLOGY, 2006, 130 (04) : 1086 - 1097
  • [4] Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin
    Ferenci, P
    Fried, MW
    Shiffman, ML
    Smith, CI
    Marinos, G
    Gonçales, FL
    Häussinger, D
    Diago, M
    Carosi, G
    Dhumeaux, D
    Craxì, A
    Chaneac, M
    Reddy, KR
    [J]. JOURNAL OF HEPATOLOGY, 2005, 43 (03) : 425 - 433
  • [5] Selection and Characterization of Hepatitis C Virus Replicons Dually Resistant to the Polymerase and Protease Inhibitors HCV-796 and Boceprevir (SCH 503034)
    Flint, Mike
    Mullen, Stanley
    Deatly, Anne M.
    Chen, Wei
    Miller, Lynn Z.
    Ralston, Robert
    Broom, Colin
    Emini, Emilio A.
    Howe, Anita Y. M.
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (02) : 401 - 411
  • [6] Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease
    Foy, E
    Li, K
    Wang, CF
    Sumpter, R
    Ikeda, M
    Lemon, SM
    Gale, M
    [J]. SCIENCE, 2003, 300 (5622) : 1145 - 1148
  • [7] Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients
    Hinrichsen, H
    Benhamou, Y
    Wedemeyer, H
    Reiser, M
    Sentjens, RE
    Calleja, JL
    Forns, X
    Erhardt, A
    Crönlein, J
    Chaves, RL
    Yong, CL
    Nehmiz, G
    Steinmann, GG
    [J]. GASTROENTEROLOGY, 2004, 127 (05) : 1347 - 1355
  • [8] Favorable cross-resistance profile of two 432 novel hepatitis C virus inhibitors, SCH-503034 and HCV-766, and enhanced anti-replicon activity mediated by the combined use of both compounds
    Howe, A. Y.
    Ralston, R.
    Chase, R.
    Tong, X.
    Skelton, A.
    Flint, M.
    Mullen, S.
    Broom, C.
    Emini, E. A.
    [J]. JOURNAL OF HEPATOLOGY, 2007, 46 : S165 - S165
  • [9] Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon α-2a (40 kd)/ribavirin therapy
    Jensen, DM
    Morgan, TR
    Marcellin, P
    Pockros, PJ
    Reddy, KR
    Hadziyannis, SJ
    Ferenci, P
    Ackrill, AM
    Willems, B
    [J]. HEPATOLOGY, 2006, 43 (05) : 954 - 960
  • [10] Naturally Occurring Dominant Resistance Mutations to Hepatitis C Virus Protease and Polymerase Inhibitors in Treatment-Naive Patients
    Kuntzen, Thomas
    Timm, Joerg
    Berical, Andrew
    Lennon, Niall
    Berlin, Aaron M.
    Young, Sarah K.
    Lee, Bongshin
    Heckerman, David
    Carlson, Jonathan
    Reyor, Laura L.
    Kleyman, Marianna
    McMahon, Cory M.
    Birch, Christopher
    Wiesch, Julian Schulze zur
    Ledlie, Timothy
    Koehrsen, Michael
    Kodira, Chinnappa
    Roberts, Andrew D.
    Lauer, Georg M.
    Rosen, Hugo R.
    Bihl, Florian
    Cerny, Andreas
    Spengler, Ulrich
    Liu, Zhimin
    Kim, Arthr Y.
    Xing, Yanming
    Schneidewind, Arne
    Madey, Margaret A.
    Fleckenstein, Jaquelyn F.
    Park, Vicki M.
    Galagan, James E.
    Nusbaum, Chad
    Walker, Bruce D.
    Lake-Bakaar, Gerond V.
    Daar, Eric S.
    Jacobson, Ira M.
    Gomperts, Edivard D.
    Edlin, Brian R.
    Donfield, Sharyne M.
    Chung, Raymond T.
    Talal, Andrew H.
    Marion, Tony
    Birren, Bruce W.
    Henn, Mattliew R.
    Allen, Todd M.
    [J]. HEPATOLOGY, 2008, 48 (06) : 1769 - 1778