Identification
- Summary
Tioguanine is a purine analogue antineoplastic agent used for the induction of remission, and for remission consolidation in patients with acute nonlymphocytic anemias.
- Brand Names
- Lanvis, Tabloid
- Generic Name
- Tioguanine
- DrugBank Accession Number
- DB00352
- Background
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Tioguanine (DB00352)
- Weight
- Average: 167.192
Monoisotopic: 167.026565875 - Chemical Formula
- C5H5N5S
- Synonyms
- 2-Amino 6MP
- 2-Amino-1,7-dihydro-6H-purine-6-thione
- 2-amino-1,9-dihydropurine-6-thione
- 2-Amino-6-mercaptopurine
- 2-Amino-6-merkaptopurin
- 2-Amino-6-purinethiol
- 2-Aminopurin-6-thiol
- 2-Aminopurine-6-thiol
- 2-Aminopurine-6(1H)-thione
- 6-Mercapto-2-aminopurine
- 6-Mercaptoguanine
- 6-TG
- 6-Thioguanine
- TG
- ThG
- Thioguanine
- Thioguanine anhydrous
- Thioguanine, anhydrous
- Tioguanin
- Tioguanina
- Tioguanine
- Tioguaninum
- External IDs
- 6-TG
- NSC 752
- NSC-752
- NSC-76504
- Wellcome U 3 B
Pharmacology
- Indication
For remission induction and remission consolidation treatment of acute nonlymphocytic leukemias.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute nonlymphocytic leukemia •••••••••••• Treatment of Nonlymphocytic acute myeloid leukemia •••••••••••• - Contraindications & Blackbox Warnings
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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 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.
Target Actions Organism ADNA intercalationHumans - Absorption
Absorption of an oral dose is incomplete and variable, averaging approximately 30% of the administered dose (range: 14% to 46%)
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
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.
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- Route of elimination
Not Available
- 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)
- Clearance
Not Available
- Adverse Effects
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Oral, mouse: LD50 = 160 mg/kg. Symptoms of overdose include nausea, vomiting, malaise, hypotension, and diaphoresis.
- Pathways
Pathway Category Thioguanine Action Pathway Drug action Thioguanine Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Thiopurine S-methyltransferase TPMT*2 (G;G) / (C;G) G Allele ADR Directly Studied The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine. Details Thiopurine S-methyltransferase TPMT*3A (A;A) / (A;G) A Allele ADR Directly Studied The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine. Details Thiopurine S-methyltransferase TPMT*3C (G;G) / (A;G) G Allele ADR Directly Studied The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine. Details Thiopurine S-methyltransferase TPMT*4A (A;A) / (A;G) G > A ADR Directly Studied The presence of this polymorphism in TPMT may be associated with an increased risk of developing rapid bone marrow suppression when treated with tioguanine. Details Thiopurine S-methyltransferase TPMT*3B Not Available c.460G>A ADR Inferred Severe myelosuppression. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Tioguanine is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Tioguanine. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Tioguanine. Acetylsalicylic acid The metabolism of Tioguanine can be decreased when combined with Acetylsalicylic acid. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Tioguanine. - Food Interactions
- Take with or without food. However, food intake may lower tioguanine serum levels.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- International/Other Brands
- Tioguanina (Induquimica) / Tioguanine (IFET)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lanvis Tablet 40 mg Oral Aspen Pharmacare Canada Inc. 1974-12-31 Not applicable Canada 
Tabloid Tablet 40 mg/1 Oral Woodward Pharma Services Llc 2022-06-30 Not applicable US 
Tabloid Tablet 40 mg/1 Oral Glaxosmithkline Inc 1984-12-18 2014-10-31 US 
Tabloid Tablet 40 mg/1 Oral Waylis Therapeutics LLC 2023-05-15 Not applicable US Tabloid Tablet 40 mg/1 Oral Aspen Global Inc. 2013-03-12 2025-03-31 US
Categories
- ATC Codes
- L01BB03 — Tioguanine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as purinethiones. These are purines in which the purine moiety bears a thioketone.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Imidazopyrimidines
- Sub Class
- Purines and purine derivatives
- Direct Parent
- Purinethiones
- Alternative Parents
- Pyrimidinethiones / Aminopyrimidines and derivatives / Imidazoles / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organosulfur compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Organic nitrogen compound / Organonitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- 2-aminopurines (CHEBI:9555)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- WIX31ZPX66
- CAS number
- 154-42-7
- InChI Key
- WYWHKKSPHMUBEB-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H5N5S/c6-5-9-3-2(4(11)10-5)7-1-8-3/h1H,(H4,6,7,8,9,10,11)
- IUPAC Name
- 2-amino-6,7-dihydro-3H-purine-6-thione
- SMILES
- NC1=NC(=S)C2=C(N1)N=CN2
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014496
- KEGG Drug
- D08603
- KEGG Compound
- C07648
- PubChem Compound
- 2723601
- PubChem Substance
- 46508170
- ChemSpider
- 2005804
- BindingDB
- 50200099
- 10485
- ChEBI
- 9555
- ChEMBL
- CHEMBL727
- ZINC
- ZINC000006382803
- Therapeutic Targets Database
- DAP000194
- PharmGKB
- PA451663
- PDBe Ligand
- DX4
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tioguanine
- PDB Entries
- 3jqa / 3rkf / 4m5m / 4xoy / 4xp3 / 5xu8
- FDA label
- Download (174 KB)
- MSDS
- Download (30.2 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Leukemia, Lymphocytic, Acute, Adult 4 4 Completed Treatment Lymphoblastic Lymphoma 1 4 Unknown Status Treatment Acute Lymphoblastic Leukemia (ALL) 1 3 Active Not Recruiting Treatment Acute Lymphoblastic Leukaemias (ALL) / Adult B Lymphoblastic Lymphoma / Ann Arbor Stage I B Lymphoblastic Lymphoma / Ann Arbor Stage II B Lymphoblastic Lymphoma / B-cell Childhood Acute Lymphoblastic Leukemia / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Childhood B Lymphoblastic Lymphoma / Down Syndrome (DS) / Hypodiploid B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive (Ph+) 1 3 Active Not Recruiting Treatment Acute Myeloid Leukemia / Down Syndrome (DS) / Myelodysplastic Syndrome / Myeloid Leukemia Associated With Down Syndrome / Myeloproliferative Neoplasms (MPNs) 1
Pharmacoeconomics
- Manufacturers
- Glaxosmithkline
- Packagers
- DSM Corp.
- GlaxoSmithKline Inc.
- Dosage Forms
Form Route Strength Tablet Oral 40 mg Tablet Oral Tablet Oral 4000000 mg Tablet Oral 40 mg/1 - Prices
Unit description Cost Unit Thioguanine tabloid 40 mg tablet 9.88USD each Tabloid tablet 9.44USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >360 °C PhysProp water solubility 36.3 mg/mL Not Available logP -0.07 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.834 mg/mL ALOGPS logP -0.36 ALOGPS logP -0.35 Chemaxon logS -2.3 ALOGPS pKa (Strongest Acidic) 10.81 Chemaxon pKa (Strongest Basic) 4.54 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 79.09 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 46.89 m3·mol-1 Chemaxon Polarizability 15.65 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8857 Blood Brain Barrier + 0.8663 Caco-2 permeable - 0.5722 P-glycoprotein substrate Non-substrate 0.7403 P-glycoprotein inhibitor I Non-inhibitor 0.9168 P-glycoprotein inhibitor II Non-inhibitor 0.9745 Renal organic cation transporter Non-inhibitor 0.8499 CYP450 2C9 substrate Non-substrate 0.8862 CYP450 2D6 substrate Non-substrate 0.8332 CYP450 3A4 substrate Non-substrate 0.7974 CYP450 1A2 substrate Inhibitor 0.7904 CYP450 2C9 inhibitor Non-inhibitor 0.6575 CYP450 2D6 inhibitor Non-inhibitor 0.8881 CYP450 2C19 inhibitor Inhibitor 0.5517 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8537 Ames test Non AMES toxic 0.7731 Carcinogenicity Non-carcinogens 0.9255 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.1583 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9743 hERG inhibition (predictor II) Non-inhibitor 0.8918
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-014i-4900000000-d9b2da47228aaa85556a Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0900000000-e1a421f72898542d681b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00lr-0900000000-9bbe3e25e6a67ee03ca7 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0159-0900000000-79bc7116a9c222b12e7f Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-053r-3900000000-dfacae9f7fd317701a22 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0le9-9600000000-3155edfca3895ca331f3 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-9000000000-c76a5d50081954af1b18 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 130.8629868 predictedDarkChem Lite v0.1.0 [M-H]- 135.287097 predictedDarkChem Lite v0.1.0 [M-H]- 130.8597868 predictedDarkChem Lite v0.1.0 [M-H]- 130.16653 predictedDeepCCS 1.0 (2019) [M+H]+ 130.3599868 predictedDarkChem Lite v0.1.0 [M+H]+ 139.0842785 predictedDarkChem Lite v0.1.0 [M+H]+ 130.5196868 predictedDarkChem Lite v0.1.0 [M+H]+ 133.45348 predictedDeepCCS 1.0 (2019) [M+Na]+ 131.3196868 predictedDarkChem Lite v0.1.0 [M+Na]+ 150.052246 predictedDarkChem Lite v0.1.0 [M+Na]+ 131.0937868 predictedDarkChem Lite v0.1.0 [M+Na]+ 142.60097 predictedDeepCCS 1.0 (2019)
Targets
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Yes
Intercalation
References
- Schwartz EL, Ishiguro K, Sartorelli AC: Induction of leukemia cell differentiation by chemotherapeutic agents. Adv Enzyme Regul. 1983;21:3-20. [Article]
- Riscoe MK, Brouns MC, Fitchen JH: Purine metabolism as a target for leukemia chemotherapy. Blood Rev. 1989 Sep;3(3):162-73. [Article]
- Sahasranaman S, Howard D, Roy S: Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. doi: 10.1007/s00228-008-0478-6. Epub 2008 May 28. [Article]
- Coulthard S, Hogarth L: The thiopurines: an update. Invest New Drugs. 2005 Dec;23(6):523-32. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Protein homodimerization activity
- Specific Function
- Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role...
- Gene Name
- HPRT1
- Uniprot ID
- P00492
- Uniprot Name
- Hypoxanthine-guanine phosphoribosyltransferase
- Molecular Weight
- 24579.155 Da
References
- Shivashankar K, Subbayya IN, Balaram H: Development of a bacterial screen for novel hypoxanthine-guanine phosphoribosyltransferase substrates. J Mol Microbiol Biotechnol. 2001 Oct;3(4):557-62. [Article]
- Horikawa K, Kawaguchi T, Ishihara S, Nagakura S, Hidaka M, Kagimoto T, Mitsuya H, Nakakuma H: Frequent detection of T cells with mutations of the hypoxanthine-guanine phosphoribosyl transferase gene in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2002 Jan 1;99(1):24-9. [Article]
- Fuscoe JC, Zimmerman LJ, Fekete A, Setzer RW, Rossiter BJ: Analysis of X-ray-induced HPRT mutations in CHO cells: insertion and deletions. Mutat Res. 1992 Oct;269(2):171-83. [Article]
- Elgemeie GH: Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites. Curr Pharm Des. 2003;9(31):2627-42. [Article]
- Suzuki M, Tsuruoka C, Kanai T, Kato T, Yatagai F, Watanabe M: Qualitative and quantitative difference in mutation induction between carbon- and neon-ion beams in normal human cells. Biol Sci Space. 2003 Dec;17(4):302-6. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Atpase activity, coupled to transmembrane movement of substances
- Specific Function
- May be an organic anion pump relevant to cellular detoxification.
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- Multidrug resistance-associated protein 4
- Molecular Weight
- 149525.33 Da
References
- Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 05, 2023 12:31