[Using distance comparison method to build pharmacophore model of epidermal growth factor receptor inhibitors].
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.


CONCLUSIONS
This method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.
Guo
Yan-shen
YS
Department of Drug Synthesis, Institute of Materia Medica, CAMS and PUMC, Beijing 100050, China.
Chu
Feng-ming
FM
Guo
Zong-ru
ZR
D015195:Drug Design; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008956:Models, Chemical; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases