The discovery of novel β-secretase inhibitors: pharmacophore modeling, virtual screening, and docking studies

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.