Affiliation:
1. Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660,1and
2. Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-40002
Abstract
ABSTRACT
BMS-200475 was recently shown to have potent antiviral activity against hepatitis B virus (50% effective concentration = 3.7 nM; 50% cytotoxic concentration = 30 μM). In metabolic studies in both HepG2 and hepatitis B virus-transfected 2.2.15 human hepatoma cell lines, the metabolism was similar, the primary products being the di- and triphosphates. The accumulation of triphosphate was rapid and detectable down to a 5 nM concentration of added drug. When cells were labeled at 25 μM, the intracellular triphosphate concentration attained 30 pmol/10
6
cells (∼30 μM). The intracellular half-life of the triphosphate was about 15 h. Compared with five other nucleoside analogs of medical interest (lamivudine, penciclovir, ganciclovir, acyclovir, and lobucavir), BMS-200475 was most efficiently phosphorylated to the triphosphate in HepG2 cells.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
103 articles.
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