调控SOCE的小分子化合物的筛选及鉴定

钙池操纵钙内流（SOCE）是一种由STIM蛋白和Orai钙离子通道共同介导的一种钙内流。它在分泌、基因转录、酶活调节、细胞生死等过程中发挥重要的作用，并与众多疾病，特别是心血管病及免疫相关疾病密切相关。由于缺乏特异性的工具药，对SOCE激活的机制及其生理作用等研究，及对SOCE相关疾病的治疗等方面都受到了极大的阻碍。因而当前SOCE领域的一个热点和难点问题是SOCE工具药物的研发。我们建立了一个灵敏而高效的药物筛选体系，以及一个更直接，更准确的药物作用分子机制鉴定系统。在此基础上，我们将筛选一些特异性SOCE工具药物；并进一步鉴定它们以及现有的工具药的作用机制。进而探讨STIM，Orai及其介导的钙信号在不同细胞中的生理功能，最终为SOCE相关疾病，如肿瘤，各种心血管及免疫疾病等，的防治等提供新的思路或靶向药物。

Mediated by STIM protein and Orai calcium channels, Store Operated Calcium entry (SOCE) is a major calcium influx pathway for most types of cells. SOCE is crucial for calcium homeostasis and many cellular functions, especially those of immune responses. It also correlates with many vascular diseases, immune deficiency diseases and different types of cancer. However, due to the lack of specific SOCE modifiers, the understanding of molecular mechanisms underlying its activation, its physiological and pathological roles are greatly hindered. To identify new SOCE modifiers, we thus set up a highly efficient drug screening system to search for new SOCE inhibitors or activators, and two molecular tools for directly dissecting corresponding mechanisms underlying their actions. With these two novel approaches, we shall be able to identify new pharmacological tools that may promote future research and drug designs in SOCE field.