【摘要】 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。更多还原

【Abstract】 The revealing of the relationship between the G-quadruplex and cancer by modern molecular biology techniques provides a new opportunity to the anti-cancer drugs research. Because of the important effect on cellular proliferation and apoptosis,the G-quadruplex in the c-myc promoter has emerged as an attractive target for anti-cancer therapeutic agents. The present article aims to highlight recent advances in the structure of G-quadruplex in the oncogene c-myc promoter and small ligands targeting the G-quadruplex. Firstly,the biological significance of c-myc G-quadruplex is introduced. Secondly,the structures of several c-myc G-quadruplexs are analyzed. Finally,the development of the small ligands targeting c-myc G-quadruplex is introduced,and the mechanism of the quadruplex-related drug candidate CX-3543 which has entered phase Ⅰ clinical trial has been explored.更多还原