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Searching for the most effective screening system to identify cell-active inhibitors of β-secretase

2004; De Gruyter; Volume: 385; Issue: 6 Linguagem: Inglês

10.1515/bc.2004.056

1437-4315

Oliver Middendorp, Urs Lüthi, Felix Hausch, Alcide Barberis,

Protein Kinase Regulation and GTPase Signaling

Abstract The β-secretase BACE1 is an attractive drug target for reducing the level of the Alzheimers disease-promoting Aβ 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.