Mercaptopurine (6-MP) and Thioguanine (6-TG) moa

Mercaptopurine and thioguanine are purine antimetabolites. Both drugs are activated by hypoxanthine-guanine phosphoribosyltransferases (HGPRTases) to toxic nucleotides that inhibit several enzymes involved in purine metabolism. Resistant tumor cells have a decreased activity of HGPRTase, or they may increase their production of alkaline phosphatases that inactivate the toxic nucleotides. 6-Mercaptopurine (6-MP) is the thiol analog of hypoxanthine. 6-MP and 6-thioguanine were the first purine analogs to prove beneficial for treating neoplastic disease. [Note: Azathioprine, an immunosuppressant, exerts its cytotoxic effects after conversion to 6-MP.] 6-MP is used principally in the maintenance of remission in acute lymphoblastic leukemia. 6-MP and its analog, azathioprine, are also beneficial in the treatment of Crohn disease.