【作者】 杨娜； 王庆河； 李凤； 程卯生；

【Author】 Yang Na,Wang Qinghe,Li Feng,Chen Maosheng (Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education,Shenyang Pharmaceutical University,Shenyang 110016,P.R.China)

【机构】 沈阳药科大学"基于靶点的药物设计与研究"教育部重点实验室；

【摘要】 目的:基于已报道的次黄嘌呤核苷酸脱氢酶(IMPDH)抑制剂构建药效团模型,结合分子对接进行虚拟筛选,以期发现新型IMPDH抑制剂。方法:利用DS软件模建药效团模型,通过最佳搜索模式进行商业数据库搜索,并结合分子对接和其它评分软件对筛选结果进行分析评价,筛选出具有新颖结构的先导化合物。结果:应用模建的定量药效团模型,结合分子对接进行二轮虚拟筛选,最终得到结构新颖的30个先导化合物。结论:本研究针对IMPDH为靶点,基于已知抑制剂的结构,构建定量药效团模型,虚拟筛选得到了结构新颖的30个先导化合物,活性测试结果良好,为设计开发新型的IMPDH抑制剂提供了帮助。更多还原

【Abstract】 OBJECTIVE:Based on the reported IMP dehydrogenase (IMPDH) inhibitors,a pharmacophore model was constructed.Virtual screening was performed through both pharmacophore and molecular docking-based database searching,which could be valuable for the discovery and development of new IMPDH inhibitors.METHOD:The pharmacophore model was developed with the aid of DS,it was used in virtual screening by optimal search of commercial database.Combined with molecular docking and scoring,the results were analyzed and evaluated,and novel lead compounds could be found.RESULTS:With quantitative pharmacophore model and molecular docking,two round of virtual screening were used to find lead compounds and finally 30 hits with novel structure were found.CONCLUSION:In this study,we aimed to find IMPDH inhibitors through ligand-based pharmacophore model and virtual screening.30 novel lead compounds were found with potent activity,providing valuable information in the design and development of new IMPDH inhibitors.更多还原