Insights into the discovery of new 5-HT1A receptor ligands:receptor based pharmacophore  

5-羟色胺1A受体配体发现新思路:基于受体的药效团(英文)

作　　者：杨志瑜[1] 吕炜[1] 田然[1] 金宏威[1] 曾慧慧[1] 

机构地区：[1]北京大学天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2009年第2期151-155,共5页中国药学（英文版）

摘　　要：5-HT1A receptor is a crucial therapeutic target for the treatment of anxiety, depression, pain, etc. Design and preparation of potent 5-HT1A receptor ligands for drug discovery has attracted extensive attention in the past few years. In this paper, a three dimensional model of human 5-HT1A receptor was constructed by means of homology modeling. And the docking of MP349 to the receptor suggested a reliable binding mode for 5-HT1A receptor ligand. Based on this ligand-receptor binding mode, an elaborate receptor structure based pharmacophore model was established, which revealed many important features responsible for ligand and 5-HT1A receptor interactions. A virtual screening experiment verified the ability of this pharmacophore model to discover true 5-HT1A receptor ligand. The results of this research would provide important information for further optimizations of 5-HT1A receptor ligands and guide related new lead discoveries.5-HT1A是治疗焦虑症、抑郁症和疼痛等精神类疾病的重要靶点。近年来寻找5-HT1A受体配体以及相关药物的发现,一直是研究的热点。本文首先采用同源模建的方法构建了一个5-HT1A受体模型,并通过与MP349进行分子对接研究,得到了一个可靠的受体-配体结合模式。在此基础上,建立了一个基于受体的药效团模型,该药效团模型包含许多配体和受体相互作用的重要特征并在后续的虚拟筛选实验中验证了这个药效团模型检验真正的5-HT1A受体配体的能力。本研究结果可用于指导今后5-HT1A配体的合成改造以及新的先导化合物的发现。

关 键 词：5-HT1A receptor Homology modeling DOCKING PHARMACOPHORE Virtual screening 

分 类 号：R91[医药卫生—药学]