Identification of small-molecule inhibitors of the Abeta-ABAD interaction.

The interaction of amyloid beta peptide (Abeta) and Abeta-binding alcohol dehydrogenase (ABAD) was recently implicated in the pathogenesis of Alzheimer's disease (AD). Using an ELISA-based screening assay, we identified frentizole, an FDA-approved immunosuppressive drug, as a novel inhibitor of the Abeta-ABAD interaction. Analysis of the frentizole structure-activity relationship led to identification of a novel benzothiazole urea with a 30-fold improvement in potency.