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Yamanaka, G. et al.

Yamanaka, Wilson, Innaimo, Bisacchi, Egli, Rinehart, Zahler, Colonno,

Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus.

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.[1]

References

Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Yamanaka, G., Wilson, T., Innaimo, S., Bisacchi, G.S., Egli, P., Rinehart, J.K., Zahler, R., Colonno, R.J. Antimicrob. Agents Chemother. (1999) [Pubmed]

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