5羟色胺2B受体小分子荧光探针的设计合成及其在肠易激综合征研究中的应用

5羟色胺2B（5-HT2B）受体参与了体内很多重要的生理反应，并且与多种疾病的发生有着密切的关系。然而，5-HT2B受体在这些疾病中，尤其是肠易激综合征疾病中确切的生理学功能和作用机制却并不十分清楚。同时，目前也鲜有针对5-HT2B受体的小分子荧光探针报道，这使得采用荧光分析法对5-HT2B受体功能的研究相当滞后。在之前的工作中，我们基于5-HT2B受体的晶体结构进行了药物设计，得到了对5-HT2B受体具有高亲和力和选择性的候选药物2B-15。同时，我们还建立了肠易激综合征的疾病模型，并对5-HT2B受体在疾病发生过程中的关键作用进行了初步的研究。在本项目中，我们将基于候选药物2B-15开发针对5-HT2B受体的小分子荧光探针，并将其应用于肠易激综合征的研究，进一步阐明5-HT2B受体在疾病发生过程中的生理功能和作用机制，进而为肠易激综合征的临床诊断和治疗提供新的途径。

5-hydroxytryptamine 2B (5-HT2B) receptors are involved in various physiological activities and thought to be associated with many diseases. However, the exact roles of 5-HT2B receptor in the disease pathogenesis are still not clear, especially for irritable bowel syndrome (IBS). Yet few fluorescent probes against 5-HT2B receptor have been reported , which limited the fluorescence analysis for this protein. Previously, we employed structure-based drug discovery techniques to explore a recently determined crystal structure of 5-HT2B receptor. A candidate drug, 2B-15, stood out with potent binding affinity and high selectivity. Besides, we also established the animial model of IBS and further confirmed the essential role of the 5-HT2B receptor in the pathogenesis of IBS. In the project, we will develop small molecule fluorescent probes against 5-HT2B receptor based on 2B-15 and apply them in the research of IBS. We wonder if we could the identify the molecular mechanism of 5-HT2B receptor and provide a new strategy for the clinical diagnosis and therapy of IBS.