Dacarbazine-d6 is intended for use as an internal standard for the quantification of dacarbazine by GC- or LC-MS. Dacarbazine is a DNA alkylating prodrug that is activated by P450 enzymes in liver microsomes.1 Following activation, it is converted, through a series of reactions, into a methyldiazonium cation that alkylates DNA at all phases of the cell cycle and induces apoptosis. In vitro, dacarbazine inhibits the growth of B16/F1, A-875, and SK-MEL-5 melanoma and non-cancerous WI-38 lung fibroblast and L-02 hepatocyte cell lines (IC50s = 260, 287, 380, 526, and 367 μM, respectively).2 Dacarbazine toxicity to 518A2 and SK-MEL-28 melanoma cell lines increases in a time-dependent manner with IC50 values of 121 and >400 μM, respectively, following a 1 hour incubation and 2.5 and 50 μM, respectively, following a 96 hour incubation.3 In vivo, dacarbazine (70 mg/kg, once every 2 days) decreases tumor volume by 59.1% in a B16/F1 murine melanoma model in mice.2 Formulations containing dacarbazine have been used in the treatment of metastatic melanoma and for Hodgkin's lymphoma in combination with other antineoplastic agents.
1.Marchesi, F., Turriziani, M., Tortorelli, G., et al.Triazene compounds: Mechanism of action and related DNA repair systemsPharmacol. Res.56(4)275-287(2007) 2.Jin, J.-l., Gong, J., Yin, T.-j., et al.PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivoEur. J. Pharmacol.654(1)17-25(2011) 3.Valiahdi, S.M., Heffeter, P., Jakupec, M.A., et al.The gallium complex KP46 exerts strong activity against primary explanted melanoma cells and induces apoptosis in melanoma cell linesMelanoma Res.19(5)283-293(2009)