Design and synthesis of selective, dual fatty acid binding protein 4 and 5 inhibitors

Bioorg Med Chem Lett. 2016 Oct 15;26(20):5092-5097. doi: 10.1016/j.bmcl.2016.08.071. Epub 2016 Aug 22.


Dual inhibition of fatty acid binding proteins 4 and 5 (FABP4 and FABP5) is expected to provide beneficial effects on a number of metabolic parameters such as insulin sensitivity and blood glucose levels and should protect against atherosclerosis. Starting from a FABP4 selective focused screening hit, biostructure information was used to modulate the selectivity profile in the desired way and to design potent dual FABP4/5 inhibitors with good selectivity against FABP3. With very good pharmacokinetic properties and no major safety alerts, compound 12 was identified as a suitable tool compound for further in vivo investigations.

Keywords: FABP4; FABP5; Quinoline derivatives; Structure-based design.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Design
  • Fatty Acid-Binding Proteins / antagonists & inhibitors*
  • Fatty Acid-Binding Proteins / chemistry
  • Mice
  • Mice, Knockout
  • Pharmacokinetics
  • Protein Conformation
  • Sequence Homology, Amino Acid


  • FABP4 protein, human
  • FABP5 protein, human
  • Fatty Acid-Binding Proteins