Temozolomide 替莫唑胺

生物活性

Temozolomide (TMZ)是一种具有口服活性的DNA损伤诱导剂，可穿过血脑屏障，并能修饰DNA环上的氮原子以及环外氧基团，以及通过甲基重氮盐中间体对DNA碱基进行甲基化，抑制DNA合成（DNA Synthesis），可用于多形性胶质母细胞瘤和黑色素瘤的相关研究。

使用AbMole产品发表的文献

• J Exp Clin Cancer Res. 2023 May 10;42(1):118.

  Piperlongumine conquers temozolomide chemoradiotherapy resistance to achieve immune cure in refractory glioblastoma via boosting oxidative stress-inflamation-CD8+-T cell immunity

• Nano Research. 2023 Jul 5.

  Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety

• Sci Adv. 2022 May 13;8(19):eabn1229.

  Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer

• Biochem Biophys Res Commun. 2021 Sep 10;569:1-9.

  Rapid tumor recurrence in a novel murine GBM surgical model is associated with Akt/PD-L1/vimentin signaling

• Cancer Lett. 2020 Jun 1;479:1-12.

  Exosome-mediated Transfer of circRNA CircNFIX Enhances Temozolomide Resistance in Glioma

• Biomedicines. 2020 Jun 4;8(6):151.

  Considering the Experimental use of Temozolomide in Glioblastoma Research

• bioRxiv. 2020 Oct.

  Connexin 43 confers chemoresistance through activating PI3K

• Cell. 2019 Jun 13;177(7):1903-1914.e14.

  Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

• Cell Death Dis. 2018 Feb 12;9(2):213.

  Autophagy mediates glucose starvationinduced glioblastoma cell quiescence and chemoresistance through coordinating cell metabolism, cell cycle, and survival

• J Clin Transl Sci. 2018 Nov 21;Vol2, Supplement S1, pp.11-12.

  2036 Extracellular matrix as a novel approach to glioma therapy

• Cancer Lett. 2016 Aug 28;379(1):134-42.

  HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

产品使用成果展示

	数据来源	Cell Death Dis (2018). Figure 3. Temozolomide (Abmole Bioscience)
	方法	Glucose starvation sensitizes glioblastoma cells to chemotherapies
	细胞系/动物模型	U87 and U251 cells
	浓度	200 μM
	处理时间	5 d
	实验结果	Treatment with either temozolomide or carboplatin induced about 50 and 80% GBM cell death under normal and glucose starvation conditions, respectively

	数据来源	Cell Death Dis (2018). Figure 1. Temozolomide (Abmole Bioscience)
	方法	Glucose starvation sensitizes glioblastoma cells to chemotherapies
	细胞系/动物模型	U87 and U251 cells
	浓度	200 μM
	处理时间	5 d
	实验结果	The cytotoxic effect was progressive and by day 5, temozolomide or carboplatin treatment caused 40–60% cell loss in U87 and U251 cells. Glucose starvation nearly doubled the cell loss to 70–90%.

	数据来源	Cancer letters (2016). Figure 6.Temozolomide was obtained from AbMole (Houston, TX, USA)
	方法	western blot
	细胞系/动物模型	U87 or U251 cells
	浓度	200 μM for U87, 50 μM for U251
	处理时间	48 h
	实验结果	TMZ treatment induces the expression of HDAC6 and EGFR (Fig. 6D). Combination use of HDAC6 inhibitors and TMZ abolishes TMZ mediated EGFR and ERK phosphorylation (Fig. 6G).

	数据来源	Cancer letters (2016). Figure 5.Temozolomide was obtained from AbMole (Houston, TX, USA)
	方法	cell viability assay and cell apotosis(flow cytometry)
	细胞系/动物模型	U87 or U251 or A172 cells
	浓度	200, 400 and 800µM or 50, 100 and 200µM or 100, 200 and 400µM
	处理时间	48 h
	实验结果	These data suggest that the combination treatment of HDAC6 inhibitors and TMZ displayed an additive therapeutic effect on glioblastoma.

	数据来源	Cancer letters (2016). Figure 3.Temozolomide was obtained from AbMole (Houston, TX, USA)
	方法	cell viability assay and cell apotosis(flow cytometry)
	细胞系/动物模型	U87 or U251 cells
	浓度	400, 800 and 1200µM or 50, 100 and 200µM
	处理时间	48 h
	实验结果	Our results suggest that the overexpression of HDAC6 in glioblastoma might be an intrinsic mechanism that confers resistance to TMZ.

实验参考

体外实验*
细胞系	A2058, A375, M238 and M249 cell lines
方法	Colony formation assay Depending on the cell line (and plating efficiency), 200–1000 cells were seeded into each well of a 6-well plate and treated as described in detail previously. In the case of primary melanoma cells, 1000 cells were seeded and let grow for 24 days in the presence or absence of drug treatment; because only small colonies formed, the stained colonies were counted under the microscope.Survival of melanoma cells after drug treatment. Five different melanoma cell lines (as indicated), as well as a culture of primary melanoma tissue cells (labeled ‘primary’) were exposed to increasing concentrations of TMZ (diamonds) or NEO212 (circles) for 48 hours, and long-term survival was determined via colony formation assay (CFA).
浓度	0, 25, 50, 75, 100µM
处理时间	48 h

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	A375 cells subcutaneous tumor growth model
配制	45% glycerol, 45% ethanol, 10% DMSO
剂量	50 mg/kg
给药处理	subcutaneous injection

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	194.15
分子式	C6H6N6O2
CAS号	85622-93-1
溶解性（25°C）	DMSO 18 mg/mL
储存条件	-20°C, protect from light, sealed
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	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

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的Km系数
	动物 A的Km系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Bauer M, et al. PLoS One. Human monocytes undergo excessive apoptosis following temozolomide activating the ATM/ATR pathway while dendritic cells and macrophages are resistant.

[2] Lin CJ, et al. PLoS One. Inhibition of mitochondria- and endoplasmic reticulum stress-mediated autophagy augments temozolomide-induced apoptosis in glioma cells.

[3] Lucio Tentori, et al. Blood . Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site

[4] Plowman J, et al. Cancer Res. Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1,3-bis(2-chloroethyl)-1-nitrosourea.