Yamanaka G, Wilson T, Innaimo S, Bisacchi G S, Egli P, Rinehart J K, Zahler R, Colonno R J
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660, USA.
Antimicrob Agents Chemother. 1999 Jan;43(1):190-3. doi: 10.1128/AAC.43.1.190.
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.
BMS-200475最近被证明对乙肝病毒具有强大的抗病毒活性（50%有效浓度 = 3.7 nM；50%细胞毒性浓度 = 30 microM）。在HepG2细胞和转染乙肝病毒的2.2.15人肝癌细胞系的代谢研究中，代谢情况相似，主要产物是二磷酸盐和三磷酸盐。三磷酸盐的积累迅速，在添加药物浓度低至5 nM时即可检测到。当细胞在25 microM浓度下标记时，细胞内三磷酸盐浓度达到30 pmol/10(6)细胞（约30 microM）。三磷酸盐在细胞内的半衰期约为15小时。与其他五种具有医学意义的核苷类似物（拉米夫定、喷昔洛韦、更昔洛韦、阿昔洛韦和洛布卡韦）相比，BMS-200475在HepG2细胞中最有效地磷酸化为三磷酸盐。
