Identification of small-molecule inhibitors of the Aβ–ABAD interaction

The interaction of amyloid beta peptide (Aβ) and Aβ-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 Aβ–ABAD interaction. Analysis of the frentizole structure–activity relationship led to identification of a novel benzothiazole urea with a 30-fold improvement in potency.

Graphical abstractSmall molecules that can prevent Aβ binding to the protein ABAD, a novel strategy for the treatment of Alzheimer’s disease, were identified by high-throughput screening and chemical synthesis.Figure optionsDownload full-size imageDownload as PowerPoint slide