Design of radiosensitizers targeting for glycolysis of hypoxic tumor based on tumor implanted chick embryo

基于移植鸡胚肿瘤的糖酵解靶向放射增敏剂的设计

• 批准号: 23591842
• 负责人: UTO Yoshihiro
• 金额: $ 3.41万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591842/
• 关键词: 放射線腫瘍学; 低酸素細胞放射線増感剤; 腫瘍移植鶏卵; 解糖系酵素; 放射線増感剤; 解糖系阻害; グルコース; 2-ニトロイミダゾール; 発育鶏卵; 低酸素腫瘍

The purpose of this research is the development of the "nitroazole-modified glucose type radiosensitizers" which gave the radiosensitizing active group to glucose used as the substrate of a glycolytic system paying attention to the hypoxic cancer cell being dependent on a glycolytic system. As contents of the research, the design and synthesis of acetylglucose-modified 2-nitroimidazole TX-2244 and its five derivatives were done, and analysis of radiosensitizing activity and its enhancing mechanism was conducted using tumor cells and a tumor-implanted chicken egg model. It was shown clearly that TX-2244 demonstrates high radiosensitizing activity as an obtained result through the prevention of intracellular uptake of glucose, the decrease of the level of intracellular NADH(s), and increase of DNA damage by radiation.

本研究的目的是开发“硝基唑修饰的葡萄糖型放射增敏剂”，该药物将放射增敏活性基团赋予用作糖酵解系统底物的葡萄糖，并关注缺氧癌细胞依赖于糖酵解系统的情况。研究内容是乙酰葡萄糖修饰的2-硝基咪唑TX-2244及其五种衍生物的设计与合成，并利用肿瘤细胞和植入肿瘤的鸡蛋模型对其放射增敏活性及其增强机制进行了分析。结果清楚地表明，TX-2244通过阻止细胞内葡萄糖的摄取、细胞内NADH水平的降低以及放射线造成的DNA损伤的增加而表现出高放射增敏活性。

项目成果

Development of antimetastatic hypoxic cytotoxin TX-2137 targeting for Akt/protein kinase B

开发针对 Akt/蛋白激酶 B 的抗转移缺氧细胞毒素 TX-2137

• 发表时间: 2013
• 作者: Yoshihiro Uto;Yoshio Endo;Hiroshi Sato;Hitoshi Hori
• 通讯作者: Hitoshi Hori