物理化学学报 >> 2008, Vol. 24 >> Issue (02): 307-312.doi: 10.3866/PKU.WHXB20080221

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基于药效团模型从中草药数据库中搜索gpIIb/IIIa受体抑制剂

李旭东; 徐筱杰; 胡娟   

  1. 北京大学化学与分子工程学院, 北京 100871; 福建中医学院, 福州 350108
  • 收稿日期:2007-09-03 修回日期:2007-11-06 发布日期:2008-01-26
  • 通讯作者: 徐筱杰; 胡娟 E-mail:xiaojxu@pku.edu.cn; huj@fjtcm.edu.cn

Discovery of Inhibitors for gpIIb/IIIa Receptor from Chinese Herbal Drugs Database by Pharmacophore-Based Virtual Searching

LI Xu-Dong; XU Xiao-Jie; HU Juan   

  1. College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China; Fujian University of Traditional Chinese Medicine, Fuzhou 350108, P. R. China
  • Received:2007-09-03 Revised:2007-11-06 Published:2008-01-26
  • Contact: XU Xiao-Jie; HU Juan E-mail:xiaojxu@pku.edu.cn; huj@fjtcm.edu.cn

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摘要： 选择20 个3,4-二氢-1(1H)-异喹啉酮类gpIIb/IIIa受体抑制剂作为训练集, 利用Catalyst软件包建立了gpIIb/IIIa受体抑制剂三维药效团模型. 探讨了药效团作用模式. 并通过建立的可靠性最佳的药效团模型(线性回归系数r=0.7715), 从中草药数据库中虚拟筛选了gpIIb/IIIa受体抑制剂, 通过实验活性测定得到了8个抑制ADP活化全血血小板聚集的IC50从40到100 μmol·L-1的化合物, 进一步证明了所建药效团模型的有效性.

关键词: 药效团模型, gpIIb/IIIa, 中草药数据库

Abstract: 3D pharmacophore model was characterized using a training set of gpIIb/IIIa inhibitors which consisted of 20 3,4-dihydro-1(1H)-isoquinolinone-based antagonists by the Catalyst program. The best models (linear r=0.7715) were used as database search queries to identify active compounds for glycoprotein IIb/IIIa receptor from the Chinese herbal drugs database (CHDD) and eight active compounds were found by further activity-determined experiment. The validity of the pharmocophore model was proved further by the experimental results.

Key words: 3D pharmacophore model, gpIIb/IIIa, Chinese herbal drugs database

MSC2000: 

  • O641