6mercaptopurine

6-Mercaptopurine (6-MP) is a purine analogue antimetabolite used in the treatment of several hematologic and inflammatory diseases. It acts as a prodrug that is converted inside cells to thioinosinic acid and other thioguanine nucleotides, which disrupt purine nucleotide synthesis and interfere with DNA and RNA production, thereby inhibiting the proliferation of rapidly dividing cells.

Clinical uses include maintenance therapy for acute lymphoblastic leukemia (ALL) in both children and adults, usually as part of multi-agent regimens. It is also employed as an immunosuppressant in inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and in various autoimmune conditions. In some settings, 6-MP is used as part of immunosuppressive regimens in organ transplantation, often in place of or with azathioprine.

Activation and metabolism are key to its effects. 6-MP is activated by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to thioinosinic acid, which is further metabolized to thioguanine nucleotides. These metabolites can be incorporated into DNA and RNA and also inhibit de novo purine synthesis. Thiopurine metabolism is influenced by TPMT (thiopurine methyltransferase) activity and by xanthine oxidase. Allopurinol, a xanthine oxidase inhibitor, can markedly raise 6-MP levels, necessitating dose adjustments.

Pharmacokinetics and monitoring require attention to bone marrow suppression and liver function. Common adverse effects include myelosuppression, hepatotoxicity, pancreatitis, and increased susceptibility to infection. Before therapy, TPMT testing is often recommended to assess risk of toxicity, and regular blood counts and liver function tests are advised during treatment.