Identification
- Summary
Temozolomide is an alkylating agent used to treat glioblastoma multiforme and refractory anaplastic astrocytoma.
- Brand Names
- Temodar, Temomedac
- Generic Name
- Temozolomide
- DrugBank Accession Number
- DB00853
- Background
Refractory anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV) are primary malignant brain tumours with poor prognosis and limited treatment options. Despite considerable genetic heterogeneity, these tumours often have impaired DNA repair systems, rendering them initially sensitive to alkylating agents, although they invariably develop resistance to these agents over time.9,11,17 Temozolomide is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; these properties allow for both oral and intravenous administration.10,13,16,17 Following initial hydrolysis, further reactions liberate a highly reactive methyl diazonium cation capable of methylating various residues on adenosine and guanine bases leading to DNA lesions and eventual apoptosis.10,16 Temozomolide as an adjunct to radiotherapy followed by maintenance dosing remains the standard of care for both Glioblastoma and refractory anaplastic astrocytoma.17
Temozolomide was granted FDA approval on August 11, 1999, as an oral capsule and subsequently on February 27, 2009, as an intravenous injection. It is currently marketed under the trademark TEMODAR® by Merck.17
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Temozolomide (DB00853)
- Weight
- Average: 194.1508
Monoisotopic: 194.055223466 - Chemical Formula
- C6H6N6O2
- Synonyms
- (S)-perillyl alcohol temozolomide
- 3-methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide
- 3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide
- 3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide
- 8-carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one
- Methazolastone
- Temozolodida
- Temozolomid
- Temozolomida
- Témozolomide
- Temozolomide
- Temozolomidum
- TMZ
- External IDs
- BRN 5547136
- CCRG 81045
- CCRG-81045
- M & B 39831
- M&B 39831
- M&B-39831
- MK-7365
- NSC 362856
- NSC-362856
- SCH 52365
- SCH-52365
Pharmacology
- Indication
Temozolomide is indicated in adult patients for the treatment of newly diagnosed glioblastoma concomitantly with radiotherapy and for use as maintenance treatment thereafter. It is also indicated for the treatment of refractory anaplastic astrocytoma in adult patients or adjuvant therapy for adults with newly diagnosed anaplastic astrocytoma.19
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Advanced melanoma ••• ••••• Maintenance of Glioblastomas •••••••••••• ••••• •••••••• ••••••••• Used as adjunct in combination to treat Glioblastomas •••••••••••• ••••• ••••• ••••••••• •••••••••••• •••••••• ••••••••• Used in combination to treat Primary cns lymphoma ••• ••••• Treatment of Refractory ewing sarcoma ••• ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Temozolomide is a prodrug of the imidazotetrazine class that requires nonenzymatic hydrolysis at physiological pH in vivo to perform alkylation of adenine/guanine residues, leading to DNA damage through futile repair cycles and eventual cell death. Temozolomide treatment is associated with myelosuppression, which is likely to be more severe in females and geriatric patients. Patients must have an ANC of ≥1.5 x 109/L and a platelet count of ≥100 x 109/L before starting therapy and must be monitored weekly during the concomitant radiotherapy phase, on days one and 22 of maintenance cycles, and weekly at any point where the ANC/platelet count falls below the specified values until recovery. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have been observed following temozolomide administration. Pneumocystis pneumonia may occur in patients undergoing treatment, and prophylaxis should be provided for patients in the concomitant phase of therapy with monitoring at all stages. Severe hepatotoxicity has also been reported, and liver testing should be performed at baseline, midway through the first cycle, before each subsequent cycle, and approximately two to four weeks after the last dose. Animal studies suggest that temozolomide has significant embryo-fetal toxicity; male and female patients should practice contraception up to three and six months following the last dose of temozolomide, respectively.17
- Mechanism of action
Glioblastoma (glioblastoma multiforme) is the most common and aggressive adult primary brain tumour, accounting for 45.6% of all primary malignant brain tumours. Primarily defined histopathologically by necrosis and microvascular proliferation (WHO grade IV classification), glioblastomas are commonly treated through radiotherapy and concomitant alkylation-based chemotherapy with temozolomide.9 Temozolomide (TMZ) is a small (194 Da) lipophilic alkylating agent of the imidazotetrazine class that is stable at acidic pH, allowing for both oral and intravenous dosing, and can cross the blood-brain barrier to affect CNS tumours.10,11,17,15 After absorption, TMZ undergoes spontaneous nonenzymatic breakdown at physiological pH to form 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC), which then reacts with water to produce 5-aminoimidazole-4-carboxamide (AIC) and a highly reactive methyl diazonium cation.10 Brain tumours such as glioblastoma typically possess a more alkaline pH than healthy tissue, favouring TMZ activation within tumour tissue.10
The methyl diazonium cation is highly reactive and methylates DNA at the N7 position of guanine (N7-MeG, 70%), the N3 position of adenine (N3-MeA, 9%), and the O6 position of guanine (O6-MeG, 6%). Although more prevalent, N7-MeG and N3-MeA are rapidly repaired by the base excision repair pathway and are not primary mediators of temozolomide toxicity, although N3-MeA lesions are lethal if not repaired. By comparison, repair of O6-MeG requires action by the suicide enzyme methylguanine-DNA methyltransferase (MGMT), which removes the methyl group to restore guanine. If not repaired by MGMT, O6-MeG mispairs with thymine, activating the DNA mismatch repair (MMR) pathway that removes the thymine (not the O6-MeG), resulting in futile cycles of repair and eventual DNA strand breaks leading to apoptosis.10 As MMR activity is crucial for temozolomide cytotoxicity, cells that have reduced or absent MGMT function and an intact MMR pathway are the most sensitive to temozolomide treatment.10,11 Glioblastomas that upregulate MGMT downregulate MMR or alter both are resistant to TMZ, leading to treatment failure.10
More recently, increased interest has also been shown in the immunomodulatory effects of TMZ, related to its myelosuppressive effects. Counterintuitively, lymphodepletion may enhance the antitumour effects of cellular immunotherapy and improve the dynamics of memory cells by altering tumour-specific versus tumour-tolerant populations. The depletion of tumour-localized immunosuppressive Treg cells may contribute to an improved response to immunotherapy. Hence, TMZ treatment may also form the backbone of immunotherapy strategies against glioblastoma in the future.12
Target Actions Organism ADNA cross-linking/alkylationHumans - Absorption
Temozolomide is rapidly and completely absorbed in the gastrointestinal tract and is stable at both acidic and neutral pH. Therefore, temozolomide may be administered both orally and intravenously with a median Tmax of one hour. Following a single oral dose of 150 mg/m2, temozolomide and its active MTIC metabolite had Cmax values of 7.5 μg/mL and 282 ng/mL and AUC values of 23.4 μg*hr/mL and 864 ng*hr/mL, respectively. Similarly, following a single 90-minute IV infusion of 150 mg/m2, temozolide and its active MTIC metabolite had Cmax values of 7.3 μg/mL and 276 ng/mL and AUC values of 24.6 μg*hr/mL and 891 ng*hr/mL, respectively. Temozolomide kinetics are linear over the range of 75-250 mg/m2/day. The median Tmax is 1 hour17
Oral temozolomide absorption is affected by food. Administration following a high-fat breakfast of 587 calories caused the mean Cmax and AUC to decrease by 32% and 9%, respectively, and the median Tmax to increase by 2-fold (from 1-2.25 hours).17
- Volume of distribution
Temozolomide has a mean apparent volume of distribution (%CV) of 0.4 (13%) L/kg.17
- Protein binding
Temozolomide plasma protein binding varies from 8-36%, with an average of around 15%.13,17 In vitro binding experiments revealed approximate dissociation constants of 0.2-0.25 and 0.12 mM for temozolomide with human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), respectively; despite the slightly higher affinity for AGP, it is likely that temozolomide is predominantly bound to HSA due to its higher serum concentration. In addition, temozolomide binding to HSA results in delayed hydrolysis and a longer half-life than in buffer (1 versus 1.8 hours).14
- Metabolism
After absorption, temozolomide undergoes nonenzymatic chemical conversion to the active metabolite 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) plus carbon dioxide and to a temozolomide acid metabolite, which occurs at physiological pH but is enhanced with increasing alkalinity.10,13,16 MTIC subsequently reacts with water to produce 5-aminoimidazole-4-carboxamide (AIC) and a highly reactive methyl diazonium cation, the active alkylating species.10,13,16 The cytochrome P450 system plays only a minor role in temozolomide metabolism. Relative to the AUC of temozolomide, the exposure to MTIC and AIC is 2.4% and 23%, respectively.17
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- Route of elimination
Roughly 38% of administered temozolomide can be recovered over seven days, with 38% in the urine and only 0.8% in the feces. The recovered material comprises mainly metabolites: unidentified polar metabolites (17%), AIC (12%), and the temozolomide acid metabolite (2.3%). Only 6% of the recovered dose represents unchanged temozolomide.17
- Half-life
Temozolomide has a mean elimination half-life of 1.8 hours.17
- Clearance
Temozolomide has a clearance of approximately 5.5 L/hr/m2.17
- Adverse Effects
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The primary dose-limiting toxicity of temozolomide is myelosuppression, which can occur with any dose but is more severe at higher doses. Patients taking high doses experienced adverse reactions, including severe and prolonged myelosuppression, infections, and death. One patient who took 2000 mg/day for five days experienced pancytopenia, pyrexia, and multi-organ failure, which resulted in death. Patients experiencing an overdose should have complete blood counts monitored and provided with supportive care as necessary.17
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
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 softwareAbacavir Temozolomide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Temozolomide is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Temozolomide. Aceclofenac Aceclofenac may decrease the excretion rate of Temozolomide which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Temozolomide which could result in a higher serum level. - Food Interactions
- Take at the same time every day.
- Take on an empty stomach. Food reduces the absorption of temozolomide and taking it on an empty stomach may reduce temozolomide associated nausea and vomiting.
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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Temozolomide Capsule 180 mg Oral TEVA Canada Limited Not applicable Not applicable Canada 
Emozolomide Accord Capsule 5 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU 
Emozolomide Accord Capsule 180 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Emozolomide Accord Capsule 140 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU Emozolomide Accord Capsule 250 mg Oral Accord Healthcare S.L.U. 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-temozolomide Capsule 180 mg Oral Accord Healthcare Inc 2012-07-25 2020-02-05 Canada Ach-temozolomide Capsule 20 mg Oral Accord Healthcare Inc 2012-07-25 Not applicable Canada Ach-temozolomide Capsule 5 mg Oral Accord Healthcare Inc 2016-01-13 Not applicable Canada Ach-temozolomide Capsule 140 mg Oral Accord Healthcare Inc 2012-07-25 Not applicable Canada Ach-temozolomide Capsule 250 mg Oral Accord Healthcare Inc 2012-07-25 Not applicable Canada
Categories
- ATC Codes
- L01AX03 — Temozolomide
- Drug Categories
- Alkylating Activity
- Alkylating Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Substrates
- Drugs that are Mainly Renally Excreted
- Imidazoles
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Noxae
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Toxic Actions
- Triazenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Imidazotetrazines
- Sub Class
- Not Available
- Direct Parent
- Imidazotetrazines
- Alternative Parents
- 2-heteroaryl carboxamides / Carbonylimidazoles / Tetrazines / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Primary carboxylic acid amides / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds show 3 more
- Substituents
- 2-heteroaryl carboxamide / Aromatic heteropolycyclic compound / Azacycle / Azole / Carboxamide group / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Imidazole-4-carbonyl group show 11 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monocarboxylic acid amide, triazene derivative, imidazotetrazine (CHEBI:72564)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- YF1K15M17Y
- CAS number
- 85622-93-1
- InChI Key
- BPEGJWRSRHCHSN-UHFFFAOYSA-N
- InChI
- InChI=1S/C6H6N6O2/c1-11-6(14)12-2-8-3(4(7)13)5(12)9-10-11/h2H,1H3,(H2,7,13)
- IUPAC Name
- 3-methyl-4-oxo-3H,4H-imidazo[4,3-d][1,2,3,5]tetrazine-8-carboxamide
- SMILES
- CN1N=NC2=C(N=CN2C1=O)C(N)=O
References
- Synthesis Reference
Shen-Chun Kuo, "Synthesis of temozolomide and analogs." U.S. Patent US20020133006, issued September 19, 2002.
US20020133006- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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 . [Article]
- Yung WK: Temozolomide in malignant gliomas. Semin Oncol. 2000 Jun;27(3 Suppl 6):27-34. [Article]
- Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000 Jul;6(7):2585-97. [Article]
- Mutter N, Stupp R: Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. [Article]
- Wirsching HG, Galanis E, Weller M: Glioblastoma. Handb Clin Neurol. 2016;134:381-97. doi: 10.1016/B978-0-12-802997-8.00023-2. [Article]
- Zhang J, Stevens MF, Bradshaw TD: Temozolomide: mechanisms of action, repair and resistance. Curr Mol Pharmacol. 2012 Jan;5(1):102-14. doi: 10.2174/1874467211205010102. [Article]
- Thomas A, Tanaka M, Trepel J, Reinhold WC, Rajapakse VN, Pommier Y: Temozolomide in the Era of Precision Medicine. Cancer Res. 2017 Feb 15;77(4):823-826. doi: 10.1158/0008-5472.CAN-16-2983. Epub 2017 Feb 3. [Article]
- Karachi A, Dastmalchi F, Mitchell DA, Rahman M: Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro Oncol. 2018 Nov 12;20(12):1566-1572. doi: 10.1093/neuonc/noy072. [Article]
- Baker SD, Wirth M, Statkevich P, Reidenberg P, Alton K, Sartorius SE, Dugan M, Cutler D, Batra V, Grochow LB, Donehower RC, Rowinsky EK: Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. Clin Cancer Res. 1999 Feb;5(2):309-17. [Article]
- Rubio-Camacho M, Encinar JA, Martinez-Tome MJ, Esquembre R, Mateo CR: The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug. Biomolecules. 2020 Jul 9;10(7). pii: biom10071015. doi: 10.3390/biom10071015. [Article]
- de Gooijer MC, de Vries NA, Buckle T, Buil LCM, Beijnen JH, Boogerd W, van Tellingen O: Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2. Neoplasia. 2018 Jul;20(7):710-720. doi: 10.1016/j.neo.2018.05.001. Epub 2018 May 28. [Article]
- Denny BJ, Wheelhouse RT, Stevens MF, Tsang LL, Slack JA: NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA. Biochemistry. 1994 Aug 9;33(31):9045-51. doi: 10.1021/bi00197a003. [Article]
- FDA Approved Drug Products: TEMODAR (temozolomide) capsules and injection [Link]
- Cayman Chemical: temozolomide MSDS [Link]
- FDA Approved Drug Products: TEMODAR (temozolomide) capsules and injection (September 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0014991
- KEGG Drug
- D06067
- PubChem Compound
- 5394
- PubChem Substance
- 46507934
- ChemSpider
- 5201
- BindingDB
- 50034562
- 37776
- ChEBI
- 72564
- ChEMBL
- CHEMBL810
- ZINC
- ZINC000001482184
- Therapeutic Targets Database
- DAP000987
- PharmGKB
- PA451609
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Temozolomide
- FDA label
- Download (67.2 KB)
- MSDS
- Download (58 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 High Grade Glioma: Glioblastoma (GBM) 1 4 Completed Treatment Primary Malignant Brain Neoplasms 1 4 Not Yet Recruiting Not Available Advanced Milignant Gliomas / Cytokine-Induced Killer Cells 1 4 Recruiting Treatment Neuroblastoma (NB) 1 3 Active Not Recruiting Treatment Brain and Central Nervous System Tumors 1
Pharmacoeconomics
- Manufacturers
- Schering corp
- Barr laboratories inc
- Packagers
- Baxter International Inc.
- Physicians Total Care Inc.
- Schering Corp.
- Schering-Plough Inc.
- University Of Iowa Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral 180 mg Capsule Oral 20.0 mg Capsule Oral 100.000 mg Capsule Oral 20.000 mg Capsule, coated Oral 5 mg Capsule, coated Oral 140 mg Capsule, coated Oral 250 mg Capsule Not applicable 5 mg/1 Capsule Oral 140 mg Injection, powder, for solution Intravenous 2.5 mg/ml Powder, for solution Intravenous 100 mg / vial Injection, powder, lyophilized, for solution Intravenous 100 mg Injection Parenteral 2.5 mg/ml Capsule Oral 100 mg/1 Capsule Oral 180 mg/1 Capsule Oral 20 mg/1 Capsule Oral 250 mg/1 Capsule Oral 5 mg/1 Injection, powder, lyophilized, for solution Intravenous 100 mg/40mL Injection, powder, lyophilized, for solution Intravenous 2.5 mg/1mL Powder 1 kg/1kg Capsule Oral 20.00 mg Capsule, coated Oral 180 mg Capsule Not applicable 180 mg/1 Capsule Not applicable 20 mg/1 Capsule Not applicable 250 mg/1 Capsule Oral 140 mg/1 Capsule, coated Oral 100 mg Capsule, coated Oral 20 mg Capsule Oral 100.0 mg Capsule Oral Capsule Oral 100.00 mg Capsule Oral 100 mg Capsule Oral 20 mg Capsule Oral 250 mg Capsule Oral 5 mg - Prices
Unit description Cost Unit Temodar 250 mg capsule 466.11USD capsule Temodar 180 mg capsule 401.53USD capsule Temodar 100 mg capsule 223.07USD capsule Temodar 20 mg capsule 44.62USD capsule Temodar 5 mg capsule 10.84USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5260291 No 1993-11-09 2013-08-11 US 
CA2476494 No 2010-04-27 2023-02-20 Canada CA2066313 No 2002-08-20 2012-04-16 Canada US6987108 No 2006-01-17 2023-09-08 US US7786118 No 2010-08-31 2023-02-21 US US8623868 No 2014-01-07 2023-02-21 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 212 °C http://www.chemspider.com/Chemical-Structure.5201.html water solubility 5.09 g/L https://hmdb.ca/metabolites/HMDB0014991 logP -1.153 https://www.ema.europa.eu/en/documents/assessment-report/temomedac-epar-public-assessment-report_en.pdf - Predicted Properties
Property Value Source logP -0.28 Chemaxon pKa (Strongest Acidic) 10.46 Chemaxon pKa (Strongest Basic) -3.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 105.94 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 47.86 m3·mol-1 Chemaxon Polarizability 16.88 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9879 Caco-2 permeable + 0.5608 P-glycoprotein substrate Non-substrate 0.7228 P-glycoprotein inhibitor I Non-inhibitor 0.9255 P-glycoprotein inhibitor II Non-inhibitor 0.9823 Renal organic cation transporter Non-inhibitor 0.8822 CYP450 2C9 substrate Non-substrate 0.7948 CYP450 2D6 substrate Non-substrate 0.8695 CYP450 3A4 substrate Non-substrate 0.5855 CYP450 1A2 substrate Non-inhibitor 0.8134 CYP450 2C9 inhibitor Non-inhibitor 0.9753 CYP450 2D6 inhibitor Non-inhibitor 0.9479 CYP450 2C19 inhibitor Non-inhibitor 0.9522 CYP450 3A4 inhibitor Non-inhibitor 0.9571 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9954 Ames test Non AMES toxic 0.5322 Carcinogenicity Non-carcinogens 0.9412 Biodegradation Not ready biodegradable 0.5172 Rat acute toxicity 2.5279 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7553 hERG inhibition (predictor II) Non-inhibitor 0.9242
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 143.3431245 predictedDarkChem Lite v0.1.0 [M-H]- 143.4899245 predictedDarkChem Lite v0.1.0 [M-H]- 139.03435 predictedDeepCCS 1.0 (2019) [M-H]- 143.3431245 predictedDarkChem Lite v0.1.0 [M-H]- 143.4899245 predictedDarkChem Lite v0.1.0 [M-H]- 143.3431245 predictedDarkChem Lite v0.1.0 [M-H]- 143.4899245 predictedDarkChem Lite v0.1.0 [M-H]- 143.3431245 predictedDarkChem Lite v0.1.0 [M-H]- 143.4899245 predictedDarkChem Lite v0.1.0 [M-H]- 143.3431245 predictedDarkChem Lite v0.1.0 [M-H]- 143.4899245 predictedDarkChem Lite v0.1.0 [M-H]- 139.03435 predictedDeepCCS 1.0 (2019) [M-H]- 139.03435 predictedDeepCCS 1.0 (2019) [M-H]- 139.03435 predictedDeepCCS 1.0 (2019) [M-H]- 139.03435 predictedDeepCCS 1.0 (2019) [M+H]+ 144.1459245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.2785245 predictedDarkChem Lite v0.1.0 [M+H]+ 141.39235 predictedDeepCCS 1.0 (2019) [M+H]+ 144.1459245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.2785245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.1459245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.2785245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.1459245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.2785245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.1459245 predictedDarkChem Lite v0.1.0 [M+H]+ 144.2785245 predictedDarkChem Lite v0.1.0 [M+H]+ 141.39235 predictedDeepCCS 1.0 (2019) [M+H]+ 141.39235 predictedDeepCCS 1.0 (2019) [M+H]+ 141.39235 predictedDeepCCS 1.0 (2019) [M+H]+ 141.39235 predictedDeepCCS 1.0 (2019) [M+Na]+ 143.8525245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.6460245 predictedDarkChem Lite v0.1.0 [M+Na]+ 149.18965 predictedDeepCCS 1.0 (2019) [M+Na]+ 143.8525245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.6460245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.8525245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.6460245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.8525245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.6460245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.8525245 predictedDarkChem Lite v0.1.0 [M+Na]+ 143.6460245 predictedDarkChem Lite v0.1.0 [M+Na]+ 149.18965 predictedDeepCCS 1.0 (2019) [M+Na]+ 149.18965 predictedDeepCCS 1.0 (2019) [M+Na]+ 149.18965 predictedDeepCCS 1.0 (2019) [M+Na]+ 149.18965 predictedDeepCCS 1.0 (2019)
Targets
References
- Zaremba T, Curtin NJ: PARP inhibitor development for systemic cancer targeting. Anticancer Agents Med Chem. 2007 Sep;7(5):515-23. [Article]
- Dinca EB, Sarkaria JN, Schroeder MA, Carlson BL, Voicu R, Gupta N, Berger MS, James CD: Bioluminescence monitoring of intracranial glioblastoma xenograft: response to primary and salvage temozolomide therapy. J Neurosurg. 2007 Sep;107(3):610-6. [Article]
- Marchesi F, Turriziani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L: Triazene compounds: mechanism of action and related DNA repair systems. Pharmacol Res. 2007 Oct;56(4):275-87. Epub 2007 Aug 9. [Article]
- 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. [Article]
- 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. [Article]
- Natelson EA, Pyatt D: Temozolomide-induced myelodysplasia. Adv Hematol. 2010;2010:760402. doi: 10.1155/2010/760402. Epub 2010 Mar 4. [Article]
- Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clin Cancer Res. 2000 Jul;6(7):2585-97. [Article]
- Zhang J, Stevens MF, Bradshaw TD: Temozolomide: mechanisms of action, repair and resistance. Curr Mol Pharmacol. 2012 Jan;5(1):102-14. doi: 10.2174/1874467211205010102. [Article]
- FDA Approved Drug Products: TEMODAR (temozolomide) capsules and injection [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- Curator comments
- In vitro experiments suggest that temozolomide binding to human serum albumin (HSA) has a Ka of ~4000-5100 M^-1 (Kd of ~0.2-0.25 mM) and that HSA is the main plasma protein binding temozolomide under physiological conditions.
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Rubio-Camacho M, Encinar JA, Martinez-Tome MJ, Esquembre R, Mateo CR: The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug. Biomolecules. 2020 Jul 9;10(7). pii: biom10071015. doi: 10.3390/biom10071015. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- Curator comments
- In vitro experiments suggest that temozolomide binding to alpha-1-acid glycoprotein (AGP) has a Ka of 8184 ± 983 M^-1 (Kd of ~0.12 mM), but that due to typical AGP plasma concentrations, AGP binding represents a small fraction of total temozolomide protein binding under physiological conditions.
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Rubio-Camacho M, Encinar JA, Martinez-Tome MJ, Esquembre R, Mateo CR: The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug. Biomolecules. 2020 Jul 9;10(7). pii: biom10071015. doi: 10.3390/biom10071015. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Inhibition of P-glycoprotein and BCRP increases brain penetration of temozolomide, suggesting that these transporters are key mediators of temozolomide efflux.
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- de Gooijer MC, de Vries NA, Buckle T, Buil LCM, Beijnen JH, Boogerd W, van Tellingen O: Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2. Neoplasia. 2018 Jul;20(7):710-720. doi: 10.1016/j.neo.2018.05.001. Epub 2018 May 28. [Article]
- Lin F, de Gooijer MC, Roig EM, Buil LC, Christner SM, Beumer JH, Wurdinger T, Beijnen JH, van Tellingen O: ABCB1, ABCG2, and PTEN determine the response of glioblastoma to temozolomide and ABT-888 therapy. Clin Cancer Res. 2014 May 15;20(10):2703-13. doi: 10.1158/1078-0432.CCR-14-0084. Epub 2014 Mar 19. [Article]
- Munoz JL, Walker ND, Scotto KW, Rameshwar P: Temozolomide competes for P-glycoprotein and contributes to chemoresistance in glioblastoma cells. Cancer Lett. 2015 Oct 10;367(1):69-75. doi: 10.1016/j.canlet.2015.07.013. Epub 2015 Jul 21. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Inhibition of P-glycoprotein and BCRP increases brain penetration of temozolomide, suggesting that these transporters are key mediators of temozolomide efflux.
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- de Gooijer MC, de Vries NA, Buckle T, Buil LCM, Beijnen JH, Boogerd W, van Tellingen O: Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2. Neoplasia. 2018 Jul;20(7):710-720. doi: 10.1016/j.neo.2018.05.001. Epub 2018 May 28. [Article]
- Lin F, de Gooijer MC, Roig EM, Buil LC, Christner SM, Beumer JH, Wurdinger T, Beijnen JH, van Tellingen O: ABCB1, ABCG2, and PTEN determine the response of glioblastoma to temozolomide and ABT-888 therapy. Clin Cancer Res. 2014 May 15;20(10):2703-13. doi: 10.1158/1078-0432.CCR-14-0084. Epub 2014 Mar 19. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54