Dacarbazine-d6

Dacarbazine-d6 is intended for use as an internal standard for the quantification of dacarbazine (Item No. 21877) by GC- or LC-MS. Dacarbazine is a DNA alkylating prodrug that is activated by P450 enzymes in liver microsomes.{21297} 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 ?M, respectively).{41584} Dacarbazine toxicity to 518A2 and SK-MEL-28 melanoma cell lines increases in a time-dependent manner with IC50 values of 121 and >400 ?M, respectively, following a 1 hour incubation and 2.5 and 50 ?M, respectively, following a 96 hour incubation.{41585} 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.{41584} Formulations containing dacarbazine have been used in the treatment of metastatic melanoma and for Hodgkin's lymphoma in combination with other antineoplastic agents.