转录因子是一类具有特殊结构、行使调控基因表达功能的重要的蛋白质分子，它们通过与基因调控区域内的同源DNA序列特异性结合从而控制细胞的生长、发育和分化。异常的转录因子活性和信号畸变对肿瘤的发生、发展、浸润和转移有重要作用。本项目计划系统开发金属铂、铱、铼配合物作为具有靶向性、抗肿瘤活性、能够实时动态监控其作用过程的转录因子抑制剂，研究其构效关系和作用机制。我们在分子水平研究配合物与靶点的亲和力和结合模式；利用细胞核提取物研究配合物对转录因子抑制活性及选择性；在细胞水平探索配合物的体外抗肿瘤活性、阻遏肿瘤细胞周期进程的能力、对转录因子核定位及信号传导通路的影响；还可以通过研究配合物与转录因子的结合、甚至与细胞器结构中的一些特异性的蛋白的结合探索其作为细胞器探针的潜力。此研究不仅可以为抗肿瘤药物的开发提供信息，还可以从分子水平和信号传导网络方面更好地了解肿瘤发生发展的机制。

Transcription factors are proteins that play a fundamental role in regulating the expression of the human genome. These proteins bind to cognate sequences within the regulatory regions of genes, thereby controlling the growth, development and differentiation of cells. Aberrat transcription factor signalling and activity can plays an important role in the tumor occurrence, development, invasion and metastasis. This project designs and synthesizes a series of platinum, iridium, rhenium complexes acting as the targeted inhibitor of transcription factor activity and displaying anti-tumor effect, the mechanism of which is capable of probed through photochemical properties. The research contents include the binding modes and affinities of the complexes with targets; the inhibitory activity and selectivity of complexes on transcription factor in nuclear extracts; the in vitro anti-tumor activity; the impact of complexes on the nuclear localization and signaling of transcription factors; the inhibitory activities on the expression of related genes as well as the repression of tumor cell cycle progression; the structural-functional relationship; the potential acting as cellular and even sub-cellular probes. The in-depth study of the anti-tumor mechanisms of these metal-based transcription factor inhibitors has significant importance on the development of anti-tumor drugs with high efficiency and selectivity, and help to understand the mechanisms of tumorigenesis from the molecular level and transcription factor signaling networks.