靶向转录因子的抗肿瘤药物研发进展  

Research and development progress of anti-tumor drug targeting transcription factors

作　　者：路明英 胡唯伟 高兴华[1] LU Mingying;HU Weiwei;GAO Xinghua(China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学,江苏南京211198

出　　处：《药学研究》2024年第1期83-88,共6页Journal of Pharmaceutical Research

基　　金：国家自然科学基金(No.82073280)。

摘　　要：转录因子(transcription factor,TF)通过与DNA链上特定结合位点的结合,转录调控信号通路中不同蛋白的表达,进而参与调控多种细胞的正常生理过程,如细胞增殖、代谢、凋亡、免疫反应和分化等。TFs的异常表达促进了肿瘤的发生发展,以TFs为靶点成为药物研发的新思路。然而,结构紊乱和结合口袋的缺乏使得靶向TFs的药物设计具有挑战性。本综述将总结靶向TFs的小分子药物开发研究进展以及一些已经取得成功的案例,以证明靶向TFs成药的可行性。Transcription factor(TF)control many normal cellular processes such as cell growth and proliferation,metabolism,apoptosis,immune response and differentiation by binding to DNA-regulatory sequences.TFs are often dysregulated in cancer and associate with initiation and progression of cancer.Therefore targeting TFs provides new ideas for the development of anticancer drugs.However,drug design targeting TFs faces challenges because of structural disorder and lack of binding pockets.This review was focused on the advances and successes in the development of small molecules targeting TFs and demonstrates feasibility of drug discovery targeting TFs and provides paradigms for the development of drugs targeting TFs.

关 键 词：转录因子 抑制剂 TF-DNA相互作用 蛋白-蛋白相互作用 PROTAC 

分 类 号：R730.3[医药卫生—肿瘤]