6thioguanine

6-thioguanine (6-TG) is a purine analogue antimetabolite in the thiopurine class of chemotherapy agents used as an immunosuppressant and anticancer drug. It is activated inside cells by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to thioinosinic acid and further to thioguanine nucleotides (TGNs). These metabolites disrupt de novo purine synthesis and are incorporated into DNA and RNA, producing cytotoxic and immunosuppressive effects.

Metabolism and pharmacogenetics play important roles in 6-TG therapy. 6-TG is metabolized by multiple enzymes, including xanthine oxidase. Variants in thiopurine methyltransferase (TPMT) and in NUDT15 influence toxicity risk, with reduced activity increasing the likelihood of myelosuppression. Because allopurinol can raise thiopurine exposure, coadministration requires careful dose adjustment or avoidance in many regimens. Therapeutic monitoring typically includes complete blood counts and liver function tests, and TPMT/NUDT15 testing is often recommended before starting therapy.

Clinical use and cautions. 6-TG has been used in the treatment of certain hematologic malignancies, including acute leukemias, and in some inflammatory bowel disease regimens as an alternative or in combination with other agents. It is less widely used than other thiopurines due to toxicity concerns, particularly hepatotoxicity and risk of veno-occlusive disease at higher doses. Dosing is generally individualized based on body weight, organ function, and metabolic genotype, with close monitoring for cytopenias and liver injury.

Adverse effects include myelosuppression, hepatotoxicity, mucositis, pancreatitis, and increased susceptibility to infections. The drug should be used under specialist supervision with appropriate pretreatment testing and ongoing safety monitoring.