Mitoguazone (Methyl-GAG) is a selective S-adenosyl-methionine decarboxylase inhibitor that penetrates the blood-brain barrier and disrupts polyamine biosynthesis. Mitoguazone is a synthetic polycarbonyl derivative with anti-tumor activity that inhibits the integration of HIV DNA into cellular DNA in monocytes and macrophages, inducing apoptosis. Mitoguazone can be used to prevent acute leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma.

At concentrations as low as 0.5 μg/mL, Mitoguazone competitively inhibits spermidine synthesis in lymphocytes. At levels of 30 μg/mL or higher, it inhibits protein synthesis and mitochondrial respiration[5].
The ability of Mitoguazone to induce apoptosis by inhibiting the polyamine pathway was evaluated in three Burkitt lymphoma cell lines (Raji, Ramos, and Daudi) and a prostate cancer cell line (MPC 3). Mitoguazone induces apoptosis in a concentration- and time-dependent manner in all tested human cancer cell lines, and triggers p53-independent programmed cell death in the human breast cancer MCF7 cell line[2].

The impact of different stages of leukemia (P388) on the pharmacokinetics of the anti-tumor drug Mitoguazone was investigated in mice. Regardless of the tumor stage under study, there was a slight reduction in the total clearance rate of Mitoguazone, reflecting a moderate increase in the AUC in the serum of leukemia-afflicted animals. Additionally, at the late tumor stage, the drug levels in the kidneys, liver, spleen, and serum were somewhat higher compared to early-stage leukemia, and were elevated to a certain extent compared to the tumor-free control[1].