WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100810
CAS#: 85622-93-1
Description: Temozolomide, also known as SCH 52365 , MB39831, and RP46161, is a triazene analog of dacarbazine with antineoplastic activity. As a cytotoxic alkylating agent, temozolomide is converted at physiologic pH to the short-lived active compound, monomethyl triazeno imidazole carboxamide (MTIC). The cytotoxicity of MTIC is due primarily to methylation of DNA at the O6 and N7 positions of guanine, resulting in inhibition of DNA replication. Unlike dacarbazine, which is metabolized to MITC only in the liver, temozolomide is metabolized to MITC at all sites. Temozolomide is administered orally and penetrates well into the central nervous system.
Hodoodo Cat#: H100810
Name: Temozolomide
CAS#: 85622-93-1
Chemical Formula: C6H6N6O2
Exact Mass: 194.06
Molecular Weight: 194.150
Elemental Analysis: C, 37.12; H, 3.11; N, 43.29; O, 16.48
Synonym: SCH-52365; SCH52365; SCH 52365; MB39831; MB-39831; MB 39831; RP46161; RP 46161; R-P46161; CCRG81045; TMZ. US brand names: Methazolastone; Temodar. Foreign brand name: Temodal
IUPAC/Chemical Name: 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide.
InChi Key: BPEGJWRSRHCHSN-UHFFFAOYSA-N
InChi Code: InChI=1S/C6H6N6O2/c1-11-6(14)12-2-8-3(4(7)13)5(12)9-10-11/h2H,1H3,(H2,7,13)
SMILES Code: O=C(C1=C(N2C=N1)N=NN(C)C2=O)N
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: According to http://en.wikipedia.org/wiki/Temozolomide, Temozolomide (brand names Temodar and Temodal Schering-Plough Corporation) is an oral alkylating agent which can be used for the treatment of Grade IV astrocytoma -- an aggressive brain tumor, also known as glioblastoma multiforme as well as Melanoma, a form of skin cancer. It is also indicated for Grade III Anaplastic Astrocytoma and not indicated for, but now used to treat oligodendroglioma brain tumors in some countries, replacing the older (and less well-tolerated) PCV (Procarbazine-Lomustine-Vincristine) regimen. The agent was developed by Malcolm Stevens and his team at Aston University in Birmingham, A derivative of imidazotetrazine, temozolomide is the prodrug of MTIC (3-methyl-(triazen-1-yl)imidazole-4-carboxamide). It has been available in the US since August 1999, and in other countries since the early 2000s. TEMODAR contains temozolomide, an imidazotetrazine derivative. The chemical name of temozolomide is 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-as-tetrazine-8-carboxamide. The material is a white to light tan/light pink powder with a molecular formula of C6H6N6O2 and a molecular weight of 194.15. The molecule is stable at acidic pH ( < 5) and labile at pH > 7; hence TEMODAR can be administered orally and intravenously. The prodrug, temozolomide, is rapidly hydrolyzed to the active 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) at neutral and alkaline pH values, with hydrolysis taking place even faster at alkaline pH. Temozolomide is available in the United States in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg & 250 mg capsules. Now also available in an IV form for people who can not swallow capsules or who have insurance that does not cover oral cancer agents!
| Biological target: | : Temozolomide is a monofunctional SN-1 alkylating agent that can modify nitrogen atoms in the DNA ring and the extracyclic oxygen group, chemically converted to MTIC and degrades to methyldiazonium cation, which transfers methyl groups to DNA at physiologic pH. A DNA damage inducer in L-1210 and L-1210/BCNU cells. Temozolomide induces apoptosis and exhibits antitumor and antiangiogenic activity. |
| In vitro activity: | In vitro IC50 inhibitory growth values for TMZ after 3 days of culture were 472 ± 14 µM for U87, 118 ± 3 µM for U373, 634 ± 23 µM for T98G, and 719 ± 12 µM for Hs683 GBM cells.Temozolomide decreased the expression levels of HIF-1α, ID-1, ID-2, and cMyc in the glioma models investigated, all of which playing major roles in angiogenesis and the switch to hypoxic metabolism. These changes could be, at least partly, responsible for the impairment of angiogenesis observed in vitro. Reference: Neoplasia. 2008 Dec; 10(12): 1383–1392. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586689/ |
| In vivo activity: | Toxicologic studies showed that no drug-related death occurred in mice treated with Temozolomide (100 or 200 mg/kg) or with NU1025 ± Temozolomide and that the maximal weight loss was 12%. All mice recovered initial body weight 1 week after treatment. Histologic studies were carried out to analyze tumor growth in the brain of untreated animals. Results indicated that lymphoma cells were microscopically evident 2 days after challenge (Figure1A) and that tumor infiltration in brain parenchyma progressively increased during the following days (Figure 1B-C). Moreover, intracranial injection of L5178Y cells was fatal in 12 to 21 days, and macroscopic evidence of tumor was observed in additional mice killed when moribund. Reference: Blood. 2002 Mar 15;99(6):2241-4. https://www.sciencedirect.com/science/article/pii/S0006497120381179?via%3Dihub |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| Soluble in DMSO, not in water | 20.8 | 107.29 |
The following data is based on the product molecular weight 194.15 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Perazzoli G, Prados J, Ortiz R, Caba O, Cabeza L, Berdasco M, Gónzalez B, Melguizo C. Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression. PLoS One. 2015 Oct 8;10(10):e0140131. doi: 10.1371/journal.pone.0140131. PMID: 26447477; PMCID: PMC4598115. 2. Mathieu V, De Nève N, Le Mercier M, Dewelle J, Gaussin JF, Dehoux M, Kiss R, Lefranc F. Combining bevacizumab with temozolomide increases the antitumor efficacy of temozolomide in a human glioblastoma orthotopic xenograft model. Neoplasia. 2008 Dec;10(12):1383-92. doi: 10.1593/neo.08928. PMID: 19048117; PMCID: PMC2586689. 3. Tentori L, Leonetti C, Scarsella M, d'Amati G, Portarena I, Zupi G, Bonmassar E, Graziani G. Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site. Blood. 2002 Mar 15;99(6):2241-4. doi: 10.1182/blood.v99.6.2241. PMID: 11877304. 4. Catapano CV, Broggini M, Erba E, Ponti M, Mariani L, Citti L, D'Incalci M. In vitro and in vivo methazolastone-induced DNA damage and repair in L-1210 leukemia sensitive and resistant to chloroethylnitrosoureas. Cancer Res. 1987 Sep 15;47(18):4884-9. PMID: 3621181. |
| In vitro protocol: | 1. Perazzoli G, Prados J, Ortiz R, Caba O, Cabeza L, Berdasco M, Gónzalez B, Melguizo C. Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression. PLoS One. 2015 Oct 8;10(10):e0140131. doi: 10.1371/journal.pone.0140131. PMID: 26447477; PMCID: PMC4598115. 2. Mathieu V, De Nève N, Le Mercier M, Dewelle J, Gaussin JF, Dehoux M, Kiss R, Lefranc F. Combining bevacizumab with temozolomide increases the antitumor efficacy of temozolomide in a human glioblastoma orthotopic xenograft model. Neoplasia. 2008 Dec;10(12):1383-92. doi: 10.1593/neo.08928. PMID: 19048117; PMCID: PMC2586689. |
| In vivo protocol: | 1. Tentori L, Leonetti C, Scarsella M, d'Amati G, Portarena I, Zupi G, Bonmassar E, Graziani G. Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site. Blood. 2002 Mar 15;99(6):2241-4. doi: 10.1182/blood.v99.6.2241. PMID: 11877304. 2. Catapano CV, Broggini M, Erba E, Ponti M, Mariani L, Citti L, D'Incalci M. In vitro and in vivo methazolastone-induced DNA damage and repair in L-1210 leukemia sensitive and resistant to chloroethylnitrosoureas. Cancer Res. 1987 Sep 15;47(18):4884-9. PMID: 3621181. |
1: Hart MG, Garside R, Rogers G, Stein K, Grant R. Temozolomide for high grade glioma. Cochrane Database Syst Rev. 2013 Apr 30;4:CD007415. doi: 10.1002/14651858.CD007415.pub2. Review. PubMed PMID: 23633341.
2: Gutenberg A, Lumenta CB, Braunsdorf WE, Sabel M, Mehdorn HM, Westphal M, Giese A. The combination of carmustine wafers and temozolomide for the treatment of malignant gliomas. A comprehensive review of the rationale and clinical experience. J Neurooncol. 2013 Jun;113(2):163-74. doi: 10.1007/s11060-013-1110-x. Epub 2013 Mar 28. Review. PubMed PMID: 23535992.
3: Hirst TC, Vesterinen HM, Sena ES, Egan KJ, Macleod MR, Whittle IR. Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted? Br J Cancer. 2013 Jan 15;108(1):64-71. doi: 10.1038/bjc.2012.504. Review. PubMed PMID: 23321511; PubMed Central PMCID: PMC3553514.
4: Grant LM, Kleiner DE, Conjeevaram HS, Vuppalanchi R, Lee WM. Clinical and histological features of idiosyncratic acute liver injury caused by temozolomide. Dig Dis Sci. 2013 May;58(5):1415-21. doi: 10.1007/s10620-012-2493-9. Epub 2012 Dec 5. Review. PubMed PMID: 23212393; PubMed Central PMCID: PMC3826911.
5: Sengupta S, Marrinan J, Frishman C, Sampath P. Impact of temozolomide on immune response during malignant glioma chemotherapy. Clin Dev Immunol. 2012;2012:831090. doi: 10.1155/2012/831090. Epub 2012 Oct 24. Review. PubMed PMID: 23133490; PubMed Central PMCID: PMC3486128.
6: De Vos FY, Gijtenbeek JM, Bleeker-Rovers CP, van Herpen CM. Pneumocystis jirovecii pneumonia prophylaxis during temozolomide treatment for high-grade gliomas. Crit Rev Oncol Hematol. 2013 Mar;85(3):373-82. doi: 10.1016/j.critrevonc.2012.08.002. Epub 2012 Aug 25. Review. PubMed PMID: 22925496.
7: Dixit S, Baker L, Walmsley V, Hingorani M. Temozolomide-related idiosyncratic and other uncommon toxicities: a systematic review. Anticancer Drugs. 2012 Nov;23(10):1099-106. Review. PubMed PMID: 22850321.
8: Scorsetti M, Alongi F, Clerici E, Navarria P, Simonelli M, Rognone E, Santoro A. Temozolomide combined with radiotherapy in the treatment of recurrent cranial meningioma previously treated with multiple surgical resections and two sessions of radiosurgery: a case report and literature review. Tumori. 2012 May-Jun;98(3):67e-71e. doi: 10.1700/1125.12413. Review. PubMed PMID: 22825521.
9: Tatar Z, Thivat E, Planchat E, Gimbergues P, Gadea E, Abrial C, Durando X. Temozolomide and unusual indications: review of literature. Cancer Treat Rev. 2013 Apr;39(2):125-35. doi: 10.1016/j.ctrv.2012.06.002. Epub 2012 Jul 19. Review. PubMed PMID: 22818211.
10: Jiang G, Li LT, Xin Y, Zhang L, Liu YQ, Zheng JN. Strategies to improve the killing of tumors using temozolomide: targeting the DNA repair protein MGMT. Curr Med Chem. 2012;19(23):3886-92. Review. PubMed PMID: 22788764.
