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Thioguanine
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DRUG INFO
Thioguanine
Drug Name:
Thioguanine
Indication: For treatment of acute nonlymphocytic leukaemia
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).
Mechanism Of Action: Thioguanine acts through its incorporation into DNA as a false purine base, and through an additional cytotoxic effect related to its incorporation into RNA. Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP). This nucleotide reaches high intracellular concentrations at therapeutic doses. TGMP interferes at several points with the synthesis of guanine nucleotides. It inhibits de novo 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. At one time, TGMP was thought to be a significant inhibitor of ATP:GMP phosphotransferase (guanylate kinase), but recent results have not shown this. Thioguanylic acid is further converted to the di- and tri-phosphates, thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP) by the same enzymes that metabolize guanine nucleotides. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and it has been argued that incorporation of such fraudulent bases contributes to the cytotoxicity of thioguanine. Thus, thioguanine has multiple metabolic effects and, at present, it is not possible to designate one major site of action. 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 net consequence of its action is a sequential blockade of the synthesis and utilization of the purine nucleotides.
Drug Category: Antimetabolites; Antineoplastic Agents; ATC:L01BB03
Brand Names/Synonyms: BW 5071; CHEMBANK1056; Guanine, Thio-; Lanvis; NSC 752; TG; THIOGUANINE; Tabloid; Thg; Thioguanine; Tioguanin; Tioguanine; Wellcome U3b; X 27
Dosage Forms: TABLETS
Absorption: Absorption of an oral dose of thioguanine in humans is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)
Interactions:
DrugBank: Interactions for Thioguanine
Interactions for Thioguanine:
There is usually complete cross-resistance between PURINETHOL (mercaptopurine) and TABLOID brand Thioguanine.
As there is in vitro evidence that aminosalicylate derivatives (e.g., olsalazine, mesalazine, or sulphasalazine)
inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent thioguanine
therapy.
Chemical IUPAC Name: 2-amino-7H-purine-6-thiol
Chemical Formula: C5H5N5S
Half Life: 80 minutes (range, 25-240 minutes)
Drug Type: Approved Drug
# Accession No: APRD00290
CAS Registry Number: 154-42-7
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Thioguanine News
(When available)
Common enzyme is a key player in DNA repair Jan 14, 2006
Biology News Net (press release), The molecular building blocks of DNA are adenine, cytosine, guanine, thymine – A, C, G, and T in the shorthand of molecular biology. ...
An "-OMICS" Glossary Dec 19, 2005
Food Consumer, ...base: one of the molecules--adenine, guanine, cytosine, thymine, or uracil--that form part of the structure of DNA or RNA molecules. ...
Synthetic Sodium Transporter Dec 28, 2005
Chemical & Engineering News Such transporters could eventually serve as sensors or antimicrobial agents. G-quadruplexes are guanine-rich structures that bind metal cations. ...
Gene Variant Puts Kids at Risk for Lung Ills From Second-Hand ... Dec 15, 2005
MedPage Today, In most people, both copies of the gene have a guanine base (G) at a key locus in 308A, but others have either one or two adenine (A) bases, the researchers ...
Analyzing Patterns in a Sequence Dec 20, 2005
SQL Server Magazine (subscription), DNA consists of sequences of four building blocks, or bases: adenosine (A), cytosine (C), guanine (G), and thymine (T). In their analyses, scientists look for ...
DNA Technologies buys into California Dec 15, 2005
Iowa City Press Citizen, Machines developed by the company can produce up to 25,000 strands per day using the four elements of DNA -- adenine, guanine, thymine and cytosine -- in any ...
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