thioguanine

Thioguanine, also known as 6-thioguanine (6-TG), is a purine analogue used as a chemotherapy and immunosuppressive agent. It belongs to the thiopurine class, which includes azathioprine and 6-mercaptopurine. As with other thiopurines, thioguanine is administered to disrupt rapidly dividing cells, notably certain leukemic cells, and to suppress immune responses in some inflammatory and autoimmune conditions.

The drug is activated inside cells by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to thioinosinic acid and, through further metabolism, to thioguanine nucleotides. These metabolites interfere with nucleic acid synthesis and function, inhibiting DNA and RNA synthesis and partly blocking de novo purine synthesis. The cytotoxic and immunosuppressive effects derive from incorporation of thioguanine nucleotides into nucleic acids and from disruption of nucleotide pools, leading to impaired cell proliferation.

Clinical use of thioguanine has declined in many settings due to safety concerns. It has been used historically in certain myeloid leukemias and, less commonly, investigated for inflammatory bowel disease. The primary limitation is a risk of severe hepatotoxicity, including veno-occlusive disease, as well as myelosuppression and mucosal toxicity. Because of these risks, thioguanine is not a first-line thiopurine in many regimens today, and dosing is individualized based on toxicity monitoring and, in some protocols, measurement of thioguanine nucleotide levels. Genotype variations affecting drug metabolism, such as TPMT and NUDT15, can influence toxicity and dosing decisions.

Drug interactions include heightened thioguanine exposure when coadministered with xanthine oxidase inhibitors (for example, allopurinol). Monitoring of blood counts, liver function, and, where available, TGNs, informs safety and efficacy during therapy.