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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

21卷

期数:

2015年01期

页码:

25-28

栏目:

基础医学

出版日期:

2015-01-20

文章信息/Info

Title:

Construction and application of pharmacophore model of SHP-2 inhibitors

文章编号:

1006-8147（2015）0-0025-04

作者:

魏会宇¹;  2;  金媛媛²;  王梅燕²;  朱立勤²; 3*

( 1.天津医科大学眼科医院药剂科, 天津医科大学眼视光学院, 天津医科大学眼科研究所, 天津 300384;2.天津医科大学药学院, 天津 300070;3.天津市第一中心医院药学部, 天津 300192)

Author(s):

 WEI Hui-yu¹; 2;  JIN Yuan-yuan²;  WANG Mei-yan²;  ZHU Li-qin²; 3

(1. Department of Pharmacy，Eye Hospital, Tianjin Medical University, School of Optometry and Ophthalmology, Tianjin Medical University, Eye Institute, Tianjin Medical University, Tianjin 300384, China; 2. School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; 3. Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China)

关键词:

计算机辅助药物设计 ;  药效团模型;  SHP-2抑制剂

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Keywords:

computer aided drug design;  pharmacophore model;  SHP-2 inhibitors

分类号:

R914.2

DOI:

-

文献标志码:

A

摘要:

目的：构建并应用蛋白酪氨酸磷酸酶 SHP-2抑制剂药效团模型。方法：应用 Discovery Studio 3.5 软件包中的基于分子共同特征 HipHop 和基于配体-受体晶体复合物 CPB 两种算法构建出 SHP-2抑制剂药效团模型，应用Receiver-operating curve (ROC)分析方法对产生的药效团模型进行验证并对ZINC数据库进行筛选，最后应用 Schrodinger Suite 2009 中的 Qikprop 模块来预测这些化合物的吸收、分布、代谢、排泄的性质，并与已报道的部分化合物作比较。结果：应用 HipHop 和 CPB 两种算法分别得到了识别活性与非活性分子能力最强的药效团模型，并且通过这两个模型筛选出了35个潜在SHP-2抑制活性的化合物，通过 ADME 预测得出设计出的化合物具有较好的ADME性质。结论：此两种药效团模型可以用于后续 SHP-2小分子药物的筛选和优化，同时采用两种药效团联合筛选的方法为计算机辅助药物设计提供了一个新的思路。

Abstract:

 

Objective: To construct pharmacophore model of SHP-2 inhibitors. Methods: Pharmacophore model of SHP-2 inhibitors was developed using 3D-QSAR

pharmacophore program of HipHop and CPB in Discovery Studio 3.5, and the validation was performed using ROC. Then pharmacophore-based virtual screening for ZINC database was applied. Finally, ADME was performed to predict properties including absorption, distribution, metabolism and excretion, which were compared with corresponding properties of reported compounds. Results: According to the program of HipHop and CPB, the pharmacophore models with the highest recognition ability between the active and non-active molecules were selected as the optimal pharmacophore models, and 35 potential inhibitors of SHP-2 were obtained. Compared with the reported SHP-2 inhibitors, these compounds showed greater potentials to function as drugs during ADME prediction. Conclusion: These two pharmacophore models can contribute to the discovery and design of new SHP-2 inhibitors. Moreover, the screening of combination of the two pharmacophore models provides a new perspective for computer aided drug design.

参考文献/References:

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相似文献/References:

[1]魏会宇,等.SHP-2抑制剂药效团模型的构建与应用[J].天津医科大学学报,2015,21(03):25.
　WEI Hui-yu,JIN Yuan-yuan,WANG Mei-yan,et al.Construction and application of pharmacophore model of SHP-2 inhibitors[J].Journal of Tianjin Medical University,2015,21(01):25.

备注/Memo

备注/Memo:

基金项目 国家自然科学基金资助项目 (81273361)

作者简介 魏会宇 (1979-)，男，硕士在读，研究方向：新药研究；通信作者：朱立勤，E-mail: zlq0713@aliyun.com。

常用功能

更新日期/Last Update: 2015-06-10