Temozolomide (Synonyms: CCRG 81045, MB 39831, Methazolastone, NSC 362856, Temodal, TMZ) |
| Catalog No.GC13667 |
Temozolomide is an oral activity alkylating agent that induces the formation of O6-methylguanine in DNA, which mispairs with thymine during the following cycle of DNA replication, leading to activation of the apoptotic pathways, Temozolomide could crosses the blood-brain barrier and is indicated for malignant gliomas and metastatic melanomas.
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Cas No.: 85622-93-1
Sample solution is provided at 25 µL, 10mM.
Temozolomide is an oral activity alkylating agent that induces the formation of O6-methylguanine in DNA, which mispairs with thymine during the following cycle of DNA replication, leading to activation of the apoptotic pathways, Temozolomide could crosses the blood-brain barrier and is indicated for malignant gliomas and metastatic melanomas [1]. Temozolomide induced cell cycle arrest at G2/M and to eventually lead to apoptosis [2]. At physiologic pH it is converted to the short-lived active compound, MTIC. MTIC is further hydrolyzed to 5-amino-imidazole-4-carboxamide (AIC) and to methylhydrazine. The cytotoxicity of Temozolomide is mediated by its addition of methyl groups at N7 and O6 sites on guanines and the O3 site on adenines in genomic DNA. Alkylation of the O6 site on guanine leads to the insertion of a thymine instead of a cytosine opposite the methylguanine during subsequent DNA replication, and this can result in cell death [3].
Lymphoma cell counts performed 72 hours after treatment showed that the IC50 of Temozolomide was 44 µM (35-58 µM) when used alone and 16 µM (12-26 µM) when combined with NU1025 [1]. A time-related response in DNA strand-break formation was observed in the U251MG glioblastoma cells treated with Temozolomide (100 µM) alone [4]. Temozolomide was particularly evident when U-118 cells were incubated with Temozolomide concentrations of >100 µM. When U-118 cells were incubated with Temozolomide (250 µM) the proliferation rate was inhibited by 43.2% [5].
Temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability [6]. In the early stage s.c. implanted SNB-75 astrocytoma model, a 400-mg/kg dose of Temozolomide administered on Day 5 produced 10 of 10 Day 54 tumor-free mice. In later staged s.c. U251 and SF-295 glioblastoma models, a single 600-mg/kg dose produced 9 of 10 Day 86 and 2 of 10 Day 40 tumor-free mice, respectively. In the latter group, a tumor growth delay of >315% was attained [7]. Treatment of CEP 6800 (30 mg/kg) with Temozolomide (17 and 34 mg/kg) resulted in 100% complete regression of U251MG tumors by day 28 versus 60% complete regression caused by Temozolomide alone [4].
References:
[1]. Tentori L, Leonetti C, Scarsella M, et al. Combined treatment with temozolomide and poly (ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site[J]. Blood, The Journal of the American Society of Hematology, 2002, 99(6): 2241-2244.
[2]. Baer J C, Freeman A A, Newlands E S, et al. Depletion of O6-alkylguanine-DNA alkyltransferase correlates with potentiation of temozolomide and CCNU toxicity in human tumour cells[J]. British journal of cancer, 1993, 67(6): 1299-1302.
[3]. Lee S Y. Temozolomide resistance in glioblastoma multiforme[J]. Genes & diseases, 2016, 3(3): 198-210.
[4]. Miknyoczki S J, Jones-Bolin S, Pritchard S, et al. Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly (ADP-ribose) polymerase inhibitor[J]. Molecular cancer therapeutics, 2003, 2(4): 371-382.
[5]. Carmo A, Carvalheiro H, Crespo I, et al. Effect of temozolomide on the U-118 glioma cell line[J]. Oncology letters, 2011, 2(6): 1165-1170.
[6]. Friedman H S, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma[J]. Clinical cancer research, 2000, 6(7): 2585-2597.
[7]. Plowman J, Waud W R, Koutsoukos A D, et al. Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1, 3-bis (2-chloroethyl)-1-nitrosourea[J]. Cancer research, 1994, 54(14): 3793-3799.
| Cell experiment [1]: | |
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Cell lines |
U-118 GBM cell line |
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Preparation Method |
Cells were subcultured every 48 h by lifting them up with a cell scrapper. The cells were then centrifuged and resuspended in fresh DMEM. For the experiments, unsynchronized cells were treated with different concentrations of Temozolomide (0, 10, 20, 100, 250 and 500 µM) for 24 and 48 h. Assays were previously performed in the presence of DMSO, which corresponded to each Temozolomide concentration. |
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Reaction Conditions |
0, 10, 20, 100, 250 and 500 µM for 24 and 48 h |
|
Applications |
The effect of Temozolomide was particularly evident when U-118 cells were incubated with Temozolomide concentrations of >100 µM. When U-118 cells were incubated with Temozolomide (250 µM) the proliferation rate was inhibited by 43.2%, as compared to that observed in the control cells. |
| Animal experiment [2]: | |
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Animal models |
Male B6D2F1 (C57BL/6 × DBA/2) mice |
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Preparation Method |
L5178Y cells (104 in 0.03 mL RPMI-1640) were then injected intracranially, through the center-middle area of the frontal bone to a 2-mm depth, using a 0.1-mL glass microsyringe and a 27-gauge disposable needle. Temozolomide was dissolved in dimethyl-sulfoxide (40 mg/mL), diluted in saline (5 mg/mL), and administered intraperitoneally on day 2 after tumor injection at 100 mg/kg or 200 mg/kg, total dose of 200 mg/kg Temozolomide was divided in 2 doses of 100 mg/kg given on days 2 and 3. |
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Dosage form |
Intraperitoneal injection, 100, 200 mg/kg |
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Applications |
Intracranial injection of NU1025, immediately before the administration of 100 or 200 mg/kg Temozolomide, significantly increased lifespans with respect to controls or to groups treated with Temozolomide only. When Temozolomide was fractionated, the ILS obtained with this schedule was higher than that observed when NU1025 was combined with a single injection of Temozolomide. |
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References: [1]: Carmo A, Carvalheiro H, Crespo I, et al. Effect of Temozolomide on the U-118 glioma cell line[J]. Oncology letters, 2011, 2(6): 1165-1170. |
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| Cas No. | 85622-93-1 | SDF | |
| Synonyms | CCRG 81045, MB 39831, Methazolastone, NSC 362856, Temodal, TMZ | ||
| Chemical Name | 3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide | ||
| Canonical SMILES | CN1C(=O)N2C=NC(=C2N=N1)C(=O)N | ||
| Formula | C6H6N6O2 | M.Wt | 194.15 |
| Solubility | ≥ 29.61mg/mL in DMSO | Storage | Store at -20°C, protect from light, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.1507 mL | 25.7533 mL | 51.5066 mL |
| 5 mM | 1.0301 mL | 5.1507 mL | 10.3013 mL |
| 10 mM | 0.5151 mL | 2.5753 mL | 5.1507 mL |
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- Purity: >98.50%
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