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

Bioorg Med Chem Lett. 2006 Sep 1;16(17):4657-60. doi: 10.1016/j.bmcl.2006.05.099. Epub 2006 Jun 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Benzothiazoles
  • Enzyme-Linked Immunosorbent Assay
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Phenylurea Compounds / chemical synthesis
  • Phenylurea Compounds / chemistry*
  • Phenylurea Compounds / pharmacology*
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Phenylurea Compounds
  • frentizole
  • Hydroxysteroid Dehydrogenases
  • 3-Hydroxyacyl CoA Dehydrogenases