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Structural Bioinformatics‐Based Identification of EGFR Inhibitor Gefitinib as a Putative Lead Compound for BACE
Author(s) -
Niu Mingshan,
Hu Jin,
Wu Sijin,
Zhang Xiaoe,
Xu Huaxi,
Zhang Yunwu,
Zhang Jie,
Yang Yongliang
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12200
Subject(s) - gefitinib , lead compound , chemistry , docking (animal) , computational biology , egfr inhibitors , identification (biology) , drug discovery , biochemistry , pharmacology , epidermal growth factor receptor , in vitro , biology , receptor , medicine , botany , nursing
β‐secretase ( BACE ‐1) is a potential target for the treatment of A lzheimer's disease ( AD ). Despite its potential, only few compounds targeting BACE have entered the clinical trials. Herein, we describe the identification of G efitinib as a potential lead compound for BACE through an integrated approach of structural bioinformatics analysis, experimental assessment and computational analysis. In particular, we performed ELISA and western analysis to assess the effect of G efitinib using N 2a human APP 695 cells. In addition, we investigated the binding mechanism of Gefitinib with BACE through molecular docking coupled with molecular dynamics simulations. The computational analyses revealed that hydrophobic contact is a major contributing factor to the binding of G efitinib with BACE . The results obtained in the study have rendered G efitinib as a putative lead compound for BACE . Further optimization studies are warranted to improve its potency and pharmacological properties against BACE for potential AD treatment.