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Details

Stereochemistry ACHIRAL
Molecular Formula C6H6N6O2
Molecular Weight 194.1508
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TEMOZOLOMIDE

SMILES

CN1N=NC2=C(N=CN2C1=O)C(N)=O

InChI

InChIKey=BPEGJWRSRHCHSN-UHFFFAOYSA-N
InChI=1S/C6H6N6O2/c1-11-6(14)12-2-8-3(4(7)13)5(12)9-10-11/h2H,1H3,(H2,7,13)

HIDE SMILES / InChI

Description

Temozolomide, (TMZ) (brand names Temodar and Temodal and Temcad) is an oral chemotherapy drug. It’s 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 not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen 1-yl)-imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be primarily due to alkylation of DNA. Alkylation (methylation) occurs mainly at the O6 and N7 positions of guanine. This methylation of guanine residues lead to single and double-strand DNA breaks and subsequent apoptotic cell death. It is suggested that the N7-methylguanine plays a critical role in the antitumor activity of the drug, as there is a correlation between the sensitivity of tumor cell lines to temozolomide and the activity of O6-alkylguanine alkyltransferase, which is the DNA repair protein that specifically removes alkyl groups at the O6 position of guanine. Cells lines that have lower levels of AGT are more sensitive to the cytotoxicity of temozolomide. 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. The DNA MMR system is involved in the formation of a number of proteins that remove methylated guanine. Evidence shows that when this repair process is targeted to the DNA strand opposite the O6-methylguanine, its inability to find the correct target leads to long-lived nicks in the DNA. 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.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

PubMed

PubMed

TitleDatePubMed
Temozolomide: a novel oral alkylating agent.
2001 Jun
New perspectives for the diagnosis and treatment of oligodendroglioma.
2001 Oct
Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study.
2002
A phase II trial of oral temozolomide in patients with metastatic renal cell cancer.
2002 Aug
Multifaceted resistance of gliomas to temozolomide.
2002 Aug
Phase I study of temozolomide in relapsed/refractory acute leukemia.
2002 Aug 1
Effect of O6-(4-bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model.
2002 Aug 10
Temozolomide-induced flare in high-grade gliomas: a new clinical entity.
2002 Jul
Promising survival and concomitant radiation plus temozolomide followed by adjuvant temozolomide.
2002 Jul 15
Treatment of newly diagnosed glioblastoma multiforme.
2002 Jul 15
Temozolomide as second-line chemotherapy for relapsed gliomas.
2002 May
Gateways to clinical trials.
2002 May
A novel drug conjugate, NEO212, targeting proneural and mesenchymal subtypes of patient-derived glioma cancer stem cells.
2016 Feb 28
Patents

Sample Use Guides

In Vivo Use Guide
4–6 week male NOD/SCID mice were implanted intracranially with 1000 chemoresistant glioma cancer stem cells (GSCs). For analysis of NEO212 efficacy, mice were implanted intracranially with 5000 USC02 or USC04 GSCs and treated subcutaneously with vehicle (45% ethanol/glycerol and 10% DMSO) or NEO212 (25 mg/kg in vehicle). Treatment was given in a cycle of 10 days on/5 days off.
Route of Administration: subcutaneously
In Vitro Use Guide
Glioma cells (5,000 cells/well), astrocytes or EC cells (10,000 cells/well) were seeded in 96-well plates. After 24 hours NEO212 was added to the cells at different concentrations (up to 150 mkM) and incubated for 72 hours.
Name Type Language
TEMOZOLOMIDE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
TEMOZOLOMIDE [INN]
Common Name English
MK-7365
Common Name English
NSC-362856
Code English
TEMOZOLOMIDE [EMA EPAR]
Common Name English
CCRG-81045
Code English
M&B-39831
Code English
M-39831
Code English
METHAZOLASTONE
Common Name English
SCH 52365
Code English
TEMOZOLOMIDE [JAN]
Common Name English
TEMOZOLOMIDE [USAN]
Common Name English
TEMOZOLOMIDE [ORANGE BOOK]
Common Name English
TEMOZOLOMIDE [WHO-DD]
Common Name English
SCH-52365
Code English
3,4-DIHYDRO-3-METHYL-4-OXOIMIDAZO(5,1-D)-AS-TETRAZINE-8-CARBOXAMIDE
Common Name English
IMIDAZO(5,1-D)-1,2,3,5-TETRAZINE-8-CARBOXAMIDE, 3,4-DIHYDRO-3-METHYL-4-OXO-
Systematic Name English
TEMOZOLOMIDE [USP-RS]
Common Name English
TEMOZOLOMIDE [MART.]
Common Name English
TEMODAL
Brand Name English
TEMOZOLOMIDE [MI]
Common Name English
M&B 39831
Code English
TEMODAR
Brand Name English
TEMOZOLOMIDE [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175558
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
WHO-ATC L01AX03
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
NDF-RT N0000000236
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMOZOLOMIDE SUN (AUTHORIZED: GLIOMA, GLIOBLASTOMA)
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMOZOLOMIDE TEVA (AUTHORIZED: GLIOMA, GLIOBLASTOMA)
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMOZOLOMIDE SANDOZ (AUTHORIZED: GLIOMA, GLIOBLASTOMA)
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMOZOLOMIDE HEXAL (AUTHORIZED: GLIOMA, GLIOBLASTOMA)
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
WHO-VATC QL01AX03
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMOMEDAC (AUTHORIZED: GLIOMA, GLIOBLASTOMA)
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMODAL (AUTHORIZED: GLIOMA, GLIOBLASTOMA)
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
LIVERTOX 932
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
EMA ASSESSMENT REPORTS TEMOZOLOMIDE ACCORD (AUTHORIZED: GLIOMA, GLIOBLASTOMA
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
Code System Code Type Description
EPA CompTox
85622-93-1
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
MESH
C047246
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
RXCUI
37776
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY RxNorm
CAS
85622-93-1
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
EVMPD
SUB10889MIG
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
ChEMBL
CHEMBL810
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
INN
6027
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
MERCK INDEX
M10552
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY Merck Index
WIKIPEDIA
TEMOZOLOMIDE
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
PUBCHEM
5394
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY SWITZERF
DRUG BANK
DB00853
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
IUPHAR
7301
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY
NCI_THESAURUS
C1244
Created by admin on Tue Mar 06 10:42:06 UTC 2018 , Edited by admin on Tue Mar 06 10:42:06 UTC 2018
PRIMARY