摘要
目的 构建表皮生长因子受体(EGFR)抑制剂的药效团模型,设计新结构类型的化合物。方法 在EGFR结构的诱导下得到抑制剂活性构象集,将13个不同结构特征的EGFR抑制剂的构象进行叠合,应用距离比较法建立合理的药效团模型;初步验证模型的有效性,对数据库进行基于三维药效团模型的搜索和分子对接。结果 得到了EGFR抑制剂的三维药效团模型,根据此模型设计了新结构类型的化合物。结论 基于三维药效团模型进行药物分子的设计,可以减少后续工作的计算量,提高先导化合物的命中率,用于指导新型的酪氨酸激酶抑制剂的设计。
Objective To build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors. Methods Thirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method. Results Validation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method. Conclusion This method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2004年第4期379-384,共6页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金(20072057)资助~~
