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Temozolomide

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Chemical Structure| 85622-93-1 同义名 : NSC 362856;CCRG 81045;Temodar. Foreign brand name: Temodal;TMZ. US brand names: Methazolastone;RP46161;SCH-52365;Temodal;Methazolastone;MB 39831;TMZ
CAS号 : 85622-93-1
货号 : A137834
分子式 : C6H6N6O2
纯度 : 98%
分子量 : 194.151
MDL号 : MFCD00866492
存储条件:

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 20 mg/mL(103.01 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

H2O: 2.5 mg/mL(12.88 mM),配合低频超声助溶

动物实验配方:

5% DMSO+30% PEG 300+water 2 mg/mL

生物活性
描述 DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of standard base pairs. DNA damages cause changes in the structure of the genetic material and prevent the replication mechanism from functioning and performing properly. Temozolomide is converted to the active metabolite 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) by non-enzymatic chemical conversion that produces DNA damage[3]. In vitro, temozolomide exhibited anti-proliferation to human malignant glioma cell lines U373MG, U87MG, and T98G with IC50 values of 40, 30 and 350 μM, respectively. Temozolomide induced apoptosis in the MGMT expressing cells occurred through AKT-Glycogen-Synthase-Kinase-3β signaling and is mediated by myelocytomatosis oncoprotein[4]. Temozolomide treatment at concentration of 100 mM for 72h increased the population at the G2/M phase and decreased the population at the G1 phase in all malignant glioma cells. In addition, temozolomide induced autophagy in U373-MG cells[5]. In vivo, administration of 40 mg/kg temozolomide significantly increased survival times in a B16F10 mouse metastatic melanoma model[6]. Treatment with temozolomide at dose of 2.5 mg/kg daily for 4 weeks resulted in a 78.30% tumor suppression, and reduced microvessel density in the glioblastoma orthotopic xenograft model[7].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A172 200 μM Function Assay 48 h increases BRCC3 mRNA expression 25337721
A172 200 μM Function Assay 48 h increases the expression of BRCA1, BRCA2, RAD51 and FANCD2 25337721
A172 200 μM Function Assay 24/72/120 h increases γH2AX foci formation time-dependently 25337721
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00611247 Leukemia, Myeloid Phase 2 Completed - United States, California ... 展开 >> Stanford University School of Medicine Stanford, California, United States, 94305 收起 <<
NCT00611247 - Completed - -
NCT00869050 Neuroendocrine Tumors Phase 2 Completed - United States, New York ... 展开 >> Columbia University Medical Center New York, New York, United States, 10032 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

5.15mL

1.03mL

0.52mL

25.75mL

5.15mL

2.58mL

51.51mL

10.30mL

5.15mL

参考文献

[1]Iorio AL, da Ros M, et al. Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma. Oncotarget. 2017 Aug 3;8(52):89595-89606.

[2]de Gooijer MC, de Vries NA, et al. Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2. Neoplasia. 2018 Jul;20(7):710-720.

[3]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. PMID: 28159862; PMCID: PMC5313339.

[4]De Salvo M, Maresca G, D'agnano I, Marchese R, Stigliano A, Gagliassi R, Brunetti E, Raza GH, De Paula U, Bucci B. Temozolomide induced c-Myc-mediated apoptosis via Akt signalling in MGMT expressing glioblastoma cells. Int J Radiat Biol. 2011 May;87(5):518-33. doi: 10.3109/09553002.2011.556173. Epub 2011 Mar 15. PMID: 21405945.

[5]Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004 Apr;11(4):448-57. doi: 10.1038/sj.cdd.4401359. PMID: 14713959.

[6]Mathieu V, Le Mercier M, De Neve N, Sauvage S, Gras T, Roland I, Lefranc F, Kiss R. Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model. J Invest Dermatol. 2007 Oct;127(10):2399-410. doi: 10.1038/sj.jid.5700869. Epub 2007 May 10. PMID: 17495956.

[7]Jo MY, Kim YG, Kim Y, Lee SJ, Kim MH, Joo KM, Kim HH, Nam DH. Combined therapy of temozolomide and ZD6474 (vandetanib) effectively reduces glioblastoma tumor volume through anti-angiogenic and anti-proliferative mechanisms. Mol Med Rep. 2012 Jul;6(1):88-92. doi: 10.3892/mmr.2012.868. Epub 2012 Apr 11. PMID: 22505191.