已上市和部分正在Ⅲ期临床开发中的多靶点激酶抑制剂抑酶谱及信号传导通路分析  

The signal transduction pathway of multi-target kinase inhibitors as anticancer agents in clinical use or in phase Ⅲ

作　　者：吴文[1] 卢骋[1] 陈思宇[1] 余聂芳[1] 

机构地区：[1]中南大学药学院分子设计与药物发现研究所,湖南长沙410013

出　　处：《药学学报》2009年第3期242-257,共16页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30772645;30873137)

摘　　要：细胞的信号传导在细胞的代谢、分化以及死亡的过程中起着重要的作用。肿瘤的发生和发展与细胞信号的过度表达有关。以蛋白激酶为靶点的抗肿瘤治疗现已成为肿瘤研究中十分活跃的领域。目前作为抗癌药物已经上市及正在临床开发中的激酶抑制剂多数为多靶点抑制剂。多靶点激酶抑制剂能够同时抑制多个细胞信号转导通路,从而使得肿瘤细胞在多个方面受到抑制。多靶点激酶抑制剂在疗效和控制耐受性方面具有一定的优势。本文对已经上市及部分正在III期临床开发中的多靶点激酶抑制剂的抑酶谱及其信号传导通路进行综述分析。Signal transduction in cells plays an important role in the process of cellular metabolism, segmentation, differentiation, biological behaviors and cell death. Direct and indirect involvement of kinases in tumor growth, metastasis and apoptosis make them the most promising targets for anticancer discovery. Most of the kinase inhibitors in clinical use or in late development stages are multi-target kinase inhibitors （MTKIs）. These MTKIs are demonstrated to exert potent anti-tumor effects through several different pathways. This review presents in the view of a medicinal chemistry point, a brief account and analysis of transduction pathways of representative MTKIs in clinical use or in late development stages.

关 键 词：肿瘤 多靶点 激酶抑制剂 信号传导通路 抗肿瘤药物 

分 类 号：R916[医药卫生—药学]