摘要
经典Wnt信号通路的异常活化与恶性肿瘤的发生与发展密切相关,β-catenin/TCF4 (T-cell factor 4)相互作用作为Wnt信号通路中的"分子开关",促进了肿瘤的转移与复发,被认为是广谱高选择性抗肿瘤药物开发的理想靶标之一。目前, PKF222-815、iCRT3/5/14、LF3和血根碱等靶向β-catenin/TCF4相互作用的抑制剂已在结直肠癌和肝癌等肿瘤的实验治疗中展现出良好的应用前景。本文将对β-catenin分子结构、生物学功能及β-catenin/TCF4相互作用抑制剂的研究进展进行综述和展望,以期为新型高选择性Wnt抑制剂的筛选与发现提供有益的借鉴和参考。
Wnt/β-catenin signaling pathway plays an important role in the proliferation,growth,invasion,and metastasis of human cancers.Moreover,β-catenin/T-cell factor 4(TCF4)interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway.Therefore,β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents.At present,most ongoing smallmolecule inhibitors targetingβ-catenin/TCF4 interaction,including PKF222-815,iCRT3/5/14,LF3,and sanguinarine,have been developed in preclinical studies for human cancer therapeutics.In this review,we summarized the research advances of up-to date inhibitors targetingβ-catenin/TCF4 interaction,including the molecular structure and cellular functions ofβ-catenin in canonical Wnt signaling pathway.This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targetingβ-catenin/TCF4 interaction for future anticancer strategy.
作者
付正豪
闫干干
戚海燕
刘晓平
陈云雨
FU Zheng-hao;YAN Gan-gan;QI Hai-yan;LIU Xiao-ping;CHEN Yun-yu(Institute for Drug Screening and Evaluation,Wannan Medical College,Wuhu 241002,China)
出处
《药学学报》
CAS
CSCD
北大核心
2021年第5期1238-1245,共8页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(81703546)
安徽省自然科学基金资助项目(1808085QH265)
安徽省高校自然科学研究重大项目(KJ2019ZD30)。
作者简介
通讯作者:陈云雨,Tel:86-553-3932414,E-mail:chenyunyu1984@163.com。
