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Searching for the most effective screening system to identify cell-active inhibitors of beta-secretase
Authors:Middendorp Oliver  Lüthi Urs  Hausch Felix  Barberis Alcide
Institution:ESBATech AG, CH-8952 Zürich-Schlieren, Switzerland. middendorp@esbatech.com
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.
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