The Discovery of Novel β‐Secretase Inhibitors: Pharmacophore Modeling, Virtual Screening, and Docking Studies
Yan Niu, Chao Ma, Hongwei Jin, Fengrong Xu, Haifei Gao, Peng Liu, Yongjian Li, Chao Wang, Guanyu Yang, Ping Xu · Chemical Biology & Drug Design · 2012
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 μm, respectively. These two moderate inhibitors could represent new potentials for the development of anti-Alzheimer's disease agents.