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随着DNAG-四链体结构的发现和现代分子生物学技术对其与癌症关系的揭示,DNAG-四链体逐渐成为抗肿瘤药物研究的新靶点。c-myc启动区G-四链体由于在细胞生长、增殖、凋亡、衰老及肿瘤形成等过程中的重要作用,成为DNAG-四链体中最受关注的序列之一。本文旨在对c-myc启动区G-四链体的结构及靶向c-mycG-四链体的小分子配体的研究进展进行综述。首先,介绍c-mycG-四链体的生物学意义;其次,对几种常用的c-mycG-四链体的结构进行解析;最后,对以c-myc为靶点的小分子配体的研究进展及其与G-四链体的作用模式进行综述,并对目前以c-mycG-四链体为靶点、已经走向临床实验的CX-3543的开发与作用机制进行介绍。
With the discovery of DNAG-quadruplex structure and the revelation of modern molecular biology technology to cancer, DNAG-quadruplex has become a new target of antineoplastic research. C-myc promoter G-quadruplex is one of the most interesting sequences in DNAG-quadruplex because of its important role in cell growth, proliferation, apoptosis, aging and tumorigenesis. This review aims to review the recent progress in the construction of G-quadruplexes in c-myc promoter and small molecule ligands targeting c-mycG-quadruplexes. Firstly, the biological significance of c-mycG-quadruplex was introduced. Secondly, the structures of several commonly used c-mycG-quadruplexes were analyzed. Finally, the structure of c-myc- The research progress and the mode of interaction with G-quadruplexes are reviewed. The development and mechanism of CX-3543, which has been targeted to c-mycG-quadruplexes and is currently in clinical trials, are reviewed.