核受体Nur77为靶标的小分子化合物抑制炎症信号通路

利用小分子化合物分析靶标的功能、结构及其作用模式，可以为重大疾病的诊断和防治提供新的药物作用靶点和新的先导结构，从而为创新药物的发现奠定重要基础。本课题基于前期研究结果，以核受体Nur77为靶标，探讨Nur77通过NF-kB信号通路抑制炎症的分子机制，利用上游因子和Nur77的关系，建立独特的筛选平台，在我们自己构建的特异靶向Nur77的小分子化合物库中寻找和确定能够通过Nur77介导抑制炎症的小分子化合物，并在不同模型的炎症小鼠中进一步证实化合物的生理功能。通过研究，有望系统阐明以Nur77为轴心的调控炎症反应的上下游因子及其相关的信号通路，为临床前研究提供新策略和新的先导化合物。

Using small compounds to analyze the functions, structures and action modes of targets may provide new drug targets and new lead structures for diagnosis and therapy of major diseases, thereby laying an important foundation for the innovative drug discovery. Based on our preliminary data, this project will first explore the molecular mechanism of nuclear receptor Nur77 mediated anti-inflammation through regulation of NF-kB signaling pathway. A unique screen platform will be further established, based on the relationship between upstream factors and Nur77, to identify small molecule compounds from a specific Nur77-targeted compound library set up in our previous study. Furthermore, the physiological functions of the compounds will be confirmed in different mouse models of inflammation. This study is expected to elucidate systematically the up-and downstream regulating factors as well as signaling pathways involved in the axis of Nur77 and inflammation, which would provide new pre-clinical strategy and novel lead compounds for inhibition of inflammation.