An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [PubChem]
Indication
For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.
Pharmacology
Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase).
Toxicity
Oral, mouse: LD50 = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.
Affected Organisms
Humans and other mammals
Biotransformation
Hepatic. First converted to 6-thioguanilyic acid (TGMP). TGMP is further converted to the di- and tri-phosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP) by the same enzymes that metabolize guanine nucleotides.
Absorption
Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)
Research Area: Cancer Biological Activity: The thiopurine drugs are purine antimetabolites widely used in the treatment of acute lymphoblastic leukemia, autoimmune disorders (e.g., Crohn’s disease, rheumatoid arthritis) and organ transplant recipients. [1]
