| Novel BACE-1 Inhibitors for Alzheimer’s Disease Research. Selection of a Focused Library |
|
Presentation: P01008 Session: Cheminformatics, Library Design and Virtual HTS - Poster SessionJanos Gerencser, Cesare Spadoni, Gyorgy Dorman, Laszlo Urge, Ferenc Darvas, Zsolt Gulyas (ComGrid Ltd.), Sandor Cseh (RecomGenex Ltd.), Andrea Baki (Gedeon Richter Ltd.) and Gyorgy Keseru (Gedeon Richter Ltd.), ComGenex, Inc. Presenting Author: Janos Gerencser, ComGenex Inc. - Hungary Alzheimer's disease (AD) is a degenerative brain disorder. AD is characterized by the extracellular deposition of insoluble amyloid plaques in the brain, which impairs the cholinergic system responsible for memory and learning. The main component of the amyloid plaques is the 39-42-amino acid β-amyloid peptide, which is excised from amyloid precursor protein (APP) by sequential action of two proteases including β-secretase (BACE-1). BACE-1, is now considered the primary drug target in AD therapy and extensive efforts started worldwide to develop selective inhibitors. The first generation inhibitors were mainly statine-based inhibitors, partially mimicking the cleavage site of APP. Now we present a non-peptidic focused library that was selected by a multi-step in silico selection algorithm from a 200,000-compound repository. This selection is based on proprietary hit compounds derived from in vitro screening of 20,000 compounds. Here, we present the selection methods, which serves as a starting point for hit-to-lead process. |