Thioguanin

Thioguanin, also known as 6-thioguanine, is a purine analog used as an antineoplastic and immunosuppressive agent. It has been employed in the treatment of certain leukemias, notably acute myeloid leukemia and acute lymphoblastic leukemia, and historically as an immunosuppressant in organ transplantation and autoimmune conditions. Because of significant toxicity, its use has declined and it is now less commonly prescribed, typically reserved for specific clinical circumstances or research settings.

Mechanism of action and metabolism: After cellular uptake, thioguanine is activated by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to thioinosinic acid and then to 6-thioguanine nucleotides (6-TGNs). These metabolites interfere with purine synthesis and are incorporated into DNA and RNA, impairing replication and cell proliferation. Thioguanine is metabolized by enzymes such as TPMT; individuals with reduced TPMT activity are at higher risk of myelosuppression due to accumulation of 6-TGN.

Administration and monitoring: Thioguanine is given orally in standardized dosing regimens tailored to disease type and patient factors, including TPMT status. Monitoring focuses on blood counts and liver function, as toxicity can be dose-limiting. The principal adverse effects are bone marrow suppression and hepatotoxicity, including nodular regenerative hyperplasia and, less commonly, veno-occlusive disease; mucositis, nausea, and increased infection risk may also occur. Patients with pre-existing liver disease or TPMT deficiency require careful dose adjustment and close monitoring.

See also: related purine analogs such as 6-mercaptopurine and azathioprine.