title: The discovery of novel β-secretase inhibitors: pharmacophore modeling, virtual screening, and docking studies.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Niu
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.forename: Fengrong
authors.initials: F
authors.lastname: Xu
authors.forename: Haifei
authors.initials: H
authors.lastname: Gao
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Guanyu
authors.initials: G
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D017434:Protein Structure, Tertiary
chemical_list: D008024:Ligands; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases