Valopicitabine -: Anti-hepatitis C virus drug RNA-directed RNA polymerase (NS5B) inhibitor

被引:15
作者
Sorbera, L. A. [1 ]
Castaner, J. [1 ]
Leeson, P. A. [1 ]
机构
[1] Prous Sci, E-08080 Barcelona, Spain
关键词
2 '-C-methyl-3 '-O-(L-valyl)cytidine; L-valine 3 '-ester with 2 '-C-methylcytidine;
D O I
10.1358/dof.2006.031.04.977853
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Chronic hepatitis C is caused by infection with the hepatitis C virus (HCV), a member of the Flaviviridae family of viruses. Currently available treatment for HCV, including the standard combination therapy with interferon and ribavirin, is often unsuccessful at eradicating infection. In addition, the therapies now used to treat chronic hepatitis C are associated with substantial side effects. Therefore, new therapeutic strategies such as the use of antiviral drugs targeted to HCV-specific viral enzymes are being explored. One such option is the RNA-directed RNA polymerase (NS5B) inhibitor valopicitabine (NM-283), an orally bioavailable prodrug of the novel ribonucleoside analogue NM-107. This compound has shown in vitro activity against HCV-related bovine viral diarrhea virus (BVDV) polymerase. In patients with HCV-1 infection, valopicitabine produced, reductions in HCV RNA viral load when administered either as monotherapy or, in combination with,pegylated interferon. When used together, valopicitabine, and interferon appear to have synergistic antiviral effects both in vitro and in vivo. The compound is generally well tolerated, with gastrointestinal effects being the most commonly observed treatment-related adverse events.
引用
收藏
页码:320 / 324
页数:5
相关论文
共 19 条
  • [1] AFDHAL N, 2004, HEPATOLOGY, V40
  • [2] AFDHAL N, 2005, 40 ANN M EUR ASS STU
  • [3] BICHKO V, 2005, 56 ANN M AM ASS STUD
  • [4] BICHKO V, 2005, 40 ANN M EUR ASS STU
  • [5] Challenges and successes in developing new therapies for hepatitis C
    De Francesco, R
    Migliaccio, G
    [J]. NATURE, 2005, 436 (7053) : 953 - 960
  • [6] First clinical results for a novel antiviral treatment for hepatitis C: A phase I/II dose escalation trial assessing tolerance, pharmacokinetics, and antiviral activity of NM283
    Godofsky, E
    Afdhal, N
    Rustgi, V
    Shick, L
    Duncan, L
    Zhou, XJ
    Chao, G
    Fang, C
    Fielman, B
    Myers, M
    Brown, NA
    [J]. JOURNAL OF HEPATOLOGY, 2004, 40 : 35 - 35
  • [7] GODOFSKY E, 2004, GASTROENTEROLOGY S2, V126
  • [8] LA COLLA P, 2004, Patent No. 2004077587
  • [9] LA COLLA P, Patent No. 1536804
  • [10] OBRIEN C, 2005, 56 ANN M AM ASS STUD