title: Structural bioinformatics-based identification of EGFR inhibitor gefitinib as a putative lead compound for BACE.
abstract: β-secretase (BACE-1) is a potential target for the treatment of Alzheimer's disease (AD). Despite its potential, only few compounds targeting BACE have entered the clinical trials. Herein, we describe the identification of Gefitinib 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 Gefitinib using N2a human APP695 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 Gefitinib with BACE. The results obtained in the study have rendered Gefitinib 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.
authors: Mingshan
authors: M
authors: Niu
authors: Jin
authors: J
authors: Hu
authors: Sijin
authors: S
authors: Wu
authors: Zhang
authors: Z
authors: Xiaoe
authors: Huaxi
authors: H
authors: Xu
authors: Yunwu
authors: Y
authors: Zhang
authors: Jie
authors: J
authors: Zhang
authors: Yongliang
authors: Y
authors: Yang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D000077156:Gefitinib