Affordable Access

Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound in a transgenic mouse model.

Authors
  • Weber, O
  • Schlemmer, K-H
  • Hartmann, E
  • Hagelschuer, Ina
  • Paessens, A
  • Graef, E
  • Deres, K
  • Goldmann, S
  • Niewoehner, U
  • Stoltefuss, J
  • Haebich, D
  • Ruebsamen-Waigmann, H
  • Wohlfeil, Stefan
Type
Published Article
Journal
Antiviral Research
Publisher
Elsevier
Publication Date
May 01, 2002
Volume
54
Issue
2
Pages
69–78
Identifiers
PMID: 12062392
Source
Medline
License
Unknown

Abstract

BAY 41-4109 is a member of a class of heteroaryl-pyrimidines that was recently identified as potent inhibitors of human hepatitis B virus (HBV) replication. We have investigated the antiviral activity of BAY 41-4109 (methyl (R)-4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoro-2-pyridinyl)-6-methyl-1,4-dihydro-pyrimidine-5-carboxylate) in HBV-transgenic mice (Tg [HBV1.3 fsX(-)3'5']). Bay 41-4109 was administered per os using different schedules (b.i.d. or t.i.d. for up to 28 days) and dosages ranging from 3 to 30 mg/kg. The compound reduced viral DNA in the liver and in the plasma dose-dependently with efficacy comparable to 3TC. In contrast to 3TC-treated mice, we found a reduction of cytoplasmic hepatitis B virus core antigen (HBcAg) in liver sections of BAY 41-4109-treated mice, which indicated a different mode of action. Pharmacokinetic studies in mice have shown rapid absorption, a bioavailability of 30% and dose-proportional plasma concentrations. We conclude that BAY 41-4109 is a new anti-HBV drug candidate.

Report this publication

Statistics

Seen <100 times