The Discovery of Novel β-Secretase Inhibitors: Pharmacophore Modeling, Virtual Screening, and Docking Studies

Autor:	Chao Ma, Guanyu Yang, Hongwei Jin, Haifei Gao, Fengrong Xu, Peng Liu, Yongjian Li, Yan Niu, Chao Wang, Ping Xu
Rok vydání:	2012
Předmět:	Pharmacology Virtual screening Chemistry Organic Chemistry Zinc database Biochemistry Combinatorial chemistry Förster resonance energy transfer Protein–ligand docking Docking (molecular) Drug Discovery β secretase Molecular Medicine Pharmacophore Biological evaluation
Zdroj:	Chemical Biology & Drug Design. 79:972-980
ISSN:	1747-0277
DOI:	10.1111/j.1747-0285.2012.01367.x
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::41e2e5b2a6ab3c3857a6229ed497b99e https://doi.org/10.1111/j.1747-0285.2012.01367.x Zobrazit plný text záznamu Plný text ve formátu PDF