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Record Information
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2020-02-26 21:40:45 UTC
Secondary Accession Numbers
  • HMDB14991
Metabolite Identification
Common NameTemozolomide
DescriptionTemozolomide, also known as TMZ or temodal, belongs to the class of organic compounds known as imidazotetrazines. These are organic polycyclic compounds containing an imidazole ring fused to a tetrazine ring. Imidazole is 5-membered ring consisting of three carbon atoms, and two nitrogen centers at the 1- and 3-positions. Tetrazine is a six-membered aromatic heterocycle made up of four nitrogen atoms and a two carbon atoms. Temozolomide (Temozolomide and Temodal) is an oral alkylating agent used for the treatment of refractory anaplastic astrocytoma -- a type of cancerous brain tumor. Temozolomide is a drug which is used for the treatment of adult patients diagnosed with anaplastic astrocytoma whose disease has progressed after therapy with nitrosourea and procarbazine, as well as concomitantly with radiation therapy for treatment of newly diagnosed glioblastoma multiforme. also used as maintenance therapy for glioblastoma multiforme. Temozolomide is an extremely weak basic (essentially neutral) compound (based on its pKa). It is also suggested that cytotoxic mechanism of temozolomide is related to the failure of the DNA MMR system to find a complementary base for methylated guanine. It is a prodrug that has little to no pharmacological activity until it is hydrolyzed in vivo to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC). It is suggested that MTIC then alkylates DNA at the N7 position of guanine, O3 position of adenosine, and O6 position of guanosine, with the most common site being the N7 position. The accumulation of these nicks lead to the inhibition of replication in the daughter cells, thereby blocking the cell cycle at the G2-M boundary. Cells lines that have lower levels of AGT are more sensitive to the cytotoxicity of temozolomide. MTIC is generated through the effect of water at the highly electropositive C4 position of temozolomide, causing the ring of temozolomide to open, release carbon dioxide, and generate MTIC. Temozolomide is not active until it is converted at physiologic pH to the active form, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC).
BRN 5547136ChEBI
m & b 39831ChEBI
MB 39831ChEBI
M&B 39831ChEBI
NSC 362856ChEBI
SCH 52365ChEBI
m And b 39831HMDB
m And b-39831HMDB
Temozolomide hexyl esterMeSH
TMZ BioshuttleMeSH
m And b39831MeSH
Chemical FormulaC6H6N6O2
Average Molecular Weight194.1508
Monoisotopic Molecular Weight194.055223466
IUPAC Name3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide
Traditional Nametemozolomide
CAS Registry Number85622-93-1
InChI Identifier
Chemical Taxonomy
Description belongs to the class of organic compounds known as imidazotetrazines. These are organic polycyclic compounds containing an imidazole ring fused to a tetrazine ring. Imidazole is 5-membered ring consisting of three carbon atoms, and two nitrogen centers at the 1- and 3-positions. Tetrazine is a six-membered aromatic heterocycle made up of four nitrogen atoms and a two carbon atoms.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
Sub ClassNot Available
Direct ParentImidazotetrazines
Alternative Parents
  • Imidazotetrazine
  • 2-heteroaryl carboxamide
  • Imidazole-4-carbonyl group
  • N-substituted imidazole
  • Tetrazine
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Carboxamide group
  • Primary carboxylic acid amide
  • Carboxylic acid derivative
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Biological location:


Industrial application:

Physical Properties
Experimental Properties
Melting Point212 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.09 g/LNot Available
LogP-2.8Not Available
Predicted Properties
Water Solubility5.09 g/LALOGPS
pKa (Strongest Acidic)10.51ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area105.94 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity47.86 m³·mol⁻¹ChemAxon
Polarizability16.88 ųChemAxon
Number of Rings2ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000f-5900000000-c57261fbff38ae5dbab0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0900000000-d9e1e206d7b06ccc479dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0f6t-0900000000-34157e6c0ae2f946b796Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-3900000000-39baca8459a2d7d69887Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0900000000-e01487cdb01c9cfbbca6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f6x-2900000000-45ff34ca952c13e2e9e1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9600000000-4719e8aa23ba0437bc9dSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Normal Concentrations
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00853 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00853 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00853
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5201
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTemozolomide
METLIN IDNot Available
PubChem Compound5394
PDB IDNot Available
ChEBI ID72564
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Yung WK: Temozolomide in malignant gliomas. Semin Oncol. 2000 Jun;27(3 Suppl 6):27-34. [PubMed:10866347 ]
  2. Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000 Jul;6(7):2585-97. [PubMed:10914698 ]
  3. Mutter N, Stupp R: Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. [PubMed:16925485 ]
  4. Wick W, Platten M, Weller M: New (alternative) temozolomide regimens for the treatment of glioma. Neuro Oncol. 2009 Feb;11(1):69-79. doi: 10.1215/15228517-2008-078. Epub 2008 Sep 4. [PubMed:18772354 ]
  5. Trinh VA, Patel SP, Hwu WJ: The safety of temozolomide in the treatment of malignancies. Expert Opin Drug Saf. 2009 Jul;8(4):493-9. doi: 10.1517/14740330902918281 . [PubMed:19435405 ]
  6. Villano JL, Seery TE, Bressler LR: Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol. 2009 Sep;64(4):647-55. doi: 10.1007/s00280-009-1050-5. Epub 2009 Jun 19. [PubMed:19543728 ]
  7. Meije Y, Lizasoain M, Garcia-Reyne A, Martinez P, Rodriguez V, Lopez-Medrano F, Juan RS, Lalueza A, Aguado JM: Emergence of cytomegalovirus disease in patients receiving temozolomide: report of two cases and literature review. Clin Infect Dis. 2010 Jun 15;50(12):e73-6. doi: 10.1086/653011. [PubMed:20455691 ]
  8. Neyns B, Tosoni A, Hwu WJ, Reardon DA: Dose-dense temozolomide regimens: antitumor activity, toxicity, and immunomodulatory effects. Cancer. 2010 Jun 15;116(12):2868-77. doi: 10.1002/cncr.25035. [PubMed:20564393 ]


General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
Uniprot ID:
Molecular weight:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]