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.
Xie
Yuli
Y
Department of Medicine, Columbia University, New York, NY 10032, USA.
Deng
Shixian
S
Chen
Zhenzhang
Z
Yan
Shidu
S
Landry
Donald W
DW
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D052160:Benzothiazoles; D004797:Enzyme-Linked Immunosorbent Assay; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010671:Phenylurea Compounds; C013997:frentizole; D006913:Hydroxysteroid Dehydrogenases; D015094:3-Hydroxyacyl CoA Dehydrogenases