4825 Tioguanine An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. 154-42-7 2723601 C5H5N5S White powder. >360°C 36.3 mg/mL Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%) Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides. 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. Half Life: When the compound was given in singles doses of 65 to 300 mg/m^2, the median plasma half-disappearance time was 80 minutes (range 25-240 minutes) Oral, mouse: LD₅₀ = 160 mg/kg. No indication of carcinogenicity to humans (not listed by IARC). For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis. 2014-09-11T05:15:51Z 2014-12-24T20:26:57Z Thioguanine C07648 9555 DB00352 DX4 true SC1=NC(=N)NC2=C1N=CN2 C5H5N5S InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11) InChIKey=WYWHKKSPHMUBEB-UHFFFAOYSA-N 167.192 167.026565875 Exogenous Solid -0.07 HMDB14496 CHEMBL727 2005804