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The Discovery of Novel β‐Secretase Inhibitors: Pharmacophore Modeling, Virtual Screening, and Docking Studies
Author(s) -
Niu Yan,
Ma Chao,
Jin Hongwei,
Xu Fengrong,
Gao Haifei,
Liu Peng,
Li Yongjian,
Wang Chao,
Yang Guanyu,
Xu Ping
Publication year - 2012
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/j.1747-0285.2012.01367.x
Subject(s) - pharmacophore , virtual screening , computational biology , docking (animal) , chemistry , drug discovery , combinatorial chemistry , stereochemistry , biochemistry , biology , medicine , nursing
This article describes the identification of two small molecular inhibitors for β‐secretase by integrating virtual screening with fluorescence resonance energy transfer bioassay. A ligand‐based pharmacophore model was developed, and the sequential virtual screening of ZINC database was performed using the acquired pharmacophore model and molecular docking. Biological evaluation of 10 virtual hits led to the identification of two novel inhibitors with IC 50 values of 4.76 and 0.31 μ m , respectively. These two moderate inhibitors could represent new potentials for the development of anti‐Alzheimer’s disease agents.