TEMOZOLOMIDE

Synonyms. Temozolomide; Temodar; 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; 3-Methyl- 4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide; 8-Carbamoyl-3-methylimidazo (5,1-d) -1,2,3,5-tetrazin-4(3H)-one; Methazolastone; Temozolodida; Temozolomidum; Temodal; Temodar;

TEMOZOLOMIDE

Click for original image

 

PRODUCT IDENTIFICATION

CAS RN

85622-93-1

EINECS RN

 

FORMULA

 C6H6N6O2

MOLE WEIGHT

194.15

H.S CODE

 2933.99.9000

SMILES

 n1(nnc2n(c1=O)cnc2C(=O)N)C

CLASSIFICATION

Imidazotetrazine alkylating agent, Antineoplastic agent

EXTRA NOTES

 Treatment of recurrent high-grade gliomas and advanced metastatic melanoma.
Temozolomide is a DNA methylating agent and drug resistance-modifying agent; anti-tumor and anti-angiogenic. Temozolomide induces G2/M arrest and apoptosis through adduction of a methyl group to O6 position of guanine in genomic DNA and functional inactivation of DNA repair protein O(6)-alkylguanine DNA alkyltransferase (AGT) in base excision repair (BER) pathway. (SigmaAldrich)

 

PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE.

white to off-white crystalline powder

MELTING POINT

210 ~ 212 C

BOILING POINT

 

DENSITY

 

SOLUBILITY IN WATER

Insoluble

SOLVENT SOLUBILITY Slightly soluble in acetone, DMSO: >20 mg/ml

VAPOR DENSITY

 

log P(octanol-water)

  

VAPOR PRESSURE

  

AUTOIGNITION TEMP

  
pK

15.29

REFRACTIVE INDEX

 

FLASH POINT

 

 
STABILITY AND REACTIVITY
STABILITY Stable under normal conditions.

INCOMPATIBLE MATERIALS

Strong oxidizing agents.

POLYMERIZATION

Has not been reported

NFPA RATINGS

Health: 2, Flammability: 0, Reactivity: 0

 

EXTERNAL LINKS & GENERAL DESCRIPTION

Wikipedia Linking - Temozolomide

Google Scholar Search - Temozolomide

Drug Information Portal (U.S. National Library of Medicine) - Temozolomide

PubChem Compound Summary - Temozolomide

Drug Bank -  Temozolomide

KEGG (Kyoto Encyclopedia of Genes and Genomes) - Temozolomide

http://www.ebi.ac.uk/ - Temozolomide

http://www.ncbi.nlm.nih.gov/ - Temozolomide

http://theoncologist.alphamedpress.org/
Temozolomide (TMZ) is the first new chemotherapy agent to be approved for the treatment of high-grade malignant gliomas in more than 20 years. This novel oral alkylating agent has demonstrated promising activity not only in brain tumors, but in a variety of solid tumors, including malignant melanoma. TMZ is 100% bioavailable when taken orally and, because of its small size and lipophilic properties, it is able to cross the blood-brain barrier. Concentrations in the central nervous system are approximately 30% of plasma concentrations. Once it has entered the central nervous system, TMZ can be spontaneously converted to the active metabolite. These pharmacologic properties make it an ideal agent for treating central nervous system malignancies. In patients with advanced metastatic melanoma, brain metastases are a major cause of treatment failure. In this setting, TMZ has been shown to be as effective as dacarbazine, with a similar safety profile. More importantly, there is evidence to suggest that TMZ-treated patients have a lower incidence of central nervous system relapse compared with dacarbazine-treated patients. Therefore, TMZ is actively being investigated for the treatment and prevention of brain metastases in melanoma patients. TMZ may become an important part of treatment regimens for advanced metastatic melanoma....

http://www.merck.com
What is TEMODAR? TEMODAR (temozolomide) is a prescription medicine used to treat adults with certain brain cancer tumors. TEMODAR blocks cell growth, especially cells that grow fast, such as cancer cells. TEMODAR may decrease the size of certain brain tumors in some patients. It is not known if TEMODAR is safe and effective in children.....

http://clincancerres.aacrjournals.org
The methylation of DNA seems to be the principal mechanism responsible for the cytotoxicity of temozolomide to malignant cells. The spontaneous conversion of temozolomide to the reactive methylating agent MTIC is initiated by the effect of water at the highly electropositive C4 position of temozolomide. This activity opens the ring, releases CO2, and generates MTIC (Fig. 1)? . The initial proposal was that this effect of water was catalyzed in the close environment of the major groove of DNA (26 , 27) , but confirming this mechanism has been difficult, and it is known that temozolomide converts readily to MTIC in free solution in the absence of DNA (2) . MTIC degrades to the methyldiazonium cation, which transfers the methyl group to DNA and to the final degradation product, AIC, which is excreted via the kidneys (28 , 29) . The methyldiazonium cation can also react with RNA and with soluble and cellular protein (23) . However, the methylation of RNA and the methylation or carbamoylation of protein do not appear to have any known significant role in the antitumor activity of temozolomide. Additional studies are required to clarify the role of these targets in the biochemical mechanism of action of temozolomide....

 

SALES SPECIFICATION

APPEARANCE

white to off-white crystalline powder

ASSAY

98.5% min

MELTING POINT

210 ~ 212 C
IMPURITY

1.0% max (total), 0.5% max (individual)

LOSS ON DRYING

1.0% max

HEAVY METALS

20ppm max
RESIDUE ON IGNITION

0.1% max

 

TRANSPORT & REGULATORY INFORMATION

UN NO.

Not regulated

HAZARD CLASS

  
PACKING GROUP  

 

SAFETY INFORMATION

HAZARD OVERVIEW

Harmful by ingestion., Irritant. May cause cancer. May impair fertility. May cause harm to the unborn child. Harmful if swallowed. Irritating to eyes, respiratory system and skin.

GHS

  

SIGNAL WORD

Danger

PICTOGRAMS

HAZARD STATEMENTS

H302-H315-H319-H335-H350-H360

P STATEMENTS

P201-P261-P305 + P351 + P338-P308 + P313

EC DIRECTIVES

 

HAZARD CODES

T

RISK PHRASES

45-46-60-61-22-36/37/38

SAFETY PHRASES

 53-26-36/37-45

 

PACKING