Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors

被引:43
|
作者
Gupta, A. K. [1 ]
Bhunia, S. S. [1 ]
Balaramnavar, V. M. [1 ]
Saxena, A. K. [1 ]
机构
[1] CSIR, Cent Drug Res Inst, Med & Proc Chem Div, Lucknow, Uttar Pradesh, India
关键词
EGFR tyrosine kinase; HER; 1; Discovery Studio; pharmacophore; docking; virtual screening; GROWTH-FACTOR RECEPTOR; POTENT INHIBITOR; SITE INHIBITORS; LUNG-CANCER; 3D QSAR; ACTIVATION; ANALOGS; BINDING; DESIGN; LIGAND;
D O I
10.1080/1062936X.2010.548830
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A pharmacophore model has been developed using diverse classes of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors useful in the treatment of human tumours. Among the top 10 generated hypotheses, the second hypothesis, with one hydrogen bond acceptor, one ring aromatic and three hydrophobic features, was found to be the best on the basis of Cat Scramble validation as well as test set prediction (rtraining = 0.89, rtest = 0.82). The model also maps well to the external test set molecules as well as clinically active molecules and corroborates the docking studies. Finally, 10 hits were identified as potential leads after virtual screening of ZINC database for EGFR TK inhibition. The study may facilitate the designing and discovery of novel EGFR TK inhibitors.
引用
收藏
页码:239 / 263
页数:25
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