title: Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus.
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 microM). 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 microM, the intracellular triphosphate concentration attained 30 pmol/10(6) cells ( approximately 30 microM). 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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660, USA. yamanaka@bms.com
authors.forename: G
authors.initials: G
authors.lastname: Yamanaka
authors.forename: T
authors.initials: T
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Innaimo
authors.forename: G S
authors.initials: GS
authors.lastname: Bisacchi
authors.forename: P
authors.initials: P
authors.lastname: Egli
authors.forename: J K
authors.initials: JK
authors.lastname: Rinehart
authors.forename: R
authors.initials: R
authors.lastname: Zahler
authors.forename: R J
authors.initials: RJ
authors.lastname: Colonno
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006207:Half-Life; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D013056:Spectrophotometry, Ultraviolet; D014162:Transfection; D014407:Tumor Cells, Cultured; D006147:Guanine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D003849:Deoxyguanosine; C413685:entecavir; D006147:Guanine