Discovery of FDA-approved drugs as inhibitors of fatty acid binding protein 4 using molecular docking screening

J Chem Inf Model. 2014 Nov 24;54(11):3046-50. doi: 10.1021/ci500503b. Epub 2014 Nov 4.

Abstract

We first identified fluorescein, ketazolam, antrafenine, darifenacin, fosaprepitant, paliperidone, risperidone, pimozide, trovafloxacin, and levofloxacin as inhibitors of fatty acid binding protein 4 using molecular docking screening from FDA-approved drugs. Subsequently, the biochemical characterizations showed that levofloxacin directly inhibited FABP4 activity in both the in vitro ligand displacement assay and cell-based function assay. Furthermore, levofloxacin did not induce adipogenesis in adipocytes, which is the major adverse effect of FABP4 inhibitors.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Approval
  • Drug Discovery*
  • Fatty Acid-Binding Proteins / antagonists & inhibitors*
  • Fatty Acid-Binding Proteins / chemistry
  • Fatty Acid-Binding Proteins / metabolism*
  • Humans
  • Ligands
  • Metabolic Diseases / drug therapy
  • Molecular Docking Simulation*
  • Protein Conformation
  • Small Molecule Libraries / metabolism*
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use
  • United States
  • United States Food and Drug Administration*

Substances

  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • Ligands
  • Small Molecule Libraries