title: Searching for the most effective screening system to identify cell-active inhibitors of beta-secretase.
abstract: The beta-secretase BACE1 is an attractive drug target for reducing the level of the Alzheimer's disease-promoting Abeta peptide in the brain. Whereas potent peptidomimetic in vitro inhibitors of BACE1 have been designed, screening approaches to identify cell-permeable small molecule inhibitors have had limited success so far. In the present minireview we summarize existing screening methods, discuss their scope of application in the drug discovery process and compare them to a novel cell-based screening system to identify BACE1 inhibitors by a positive yeast growth selection.
authors.affiliation: ESBATech AG, CH-8952 Zürich-Schlieren, Switzerland. middendorp@esbatech.com
authors.forename: Oliver
authors.initials: O
authors.lastname: Middendorp
authors.forename: Urs
authors.initials: U
authors.lastname: Lüthi
authors.forename: Felix
authors.initials: F
authors.lastname: Hausch
authors.forename: Alcide
authors.initials: A
authors.lastname: Barberis
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D010450:Endopeptidases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015003:Yeasts / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases