Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target

Fredik Lehmann; Saba Haile; Eva Axen; Carmen Medina; Jonas Uppenberg; Stefan Svensson; Thomas Lundbäck; Lena Rondahl; Tjeerd Barf

doi:10.1016/j.bmcl.2004.06.057

Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target

Bioorg Med Chem Lett. 2004 Sep 6;14(17):4445-8. doi: 10.1016/j.bmcl.2004.06.057.

Authors

Fredik Lehmann¹, Saba Haile, Eva Axen, Carmen Medina, Jonas Uppenberg, Stefan Svensson, Thomas Lundbäck, Lena Rondahl, Tjeerd Barf

Affiliation

¹ Department of Medicinal Chemistry, Biovitrum AB, SE-751 37 Uppsala, Sweden.

PMID: 15357969
DOI: 10.1016/j.bmcl.2004.06.057

Abstract

Low micromolar human A-FABP inhibitors were found by utilizing a fluorescence polarization assay, X-ray crystallography and modeling. The carbazole- and indole-based inhibitors displayed approximately 10-fold preferences over human H-FABP and E-FABP, and are highly selective against I-FABP. This communication describes the SAR for drug-like synthetic inhibitors of human A-FABP.

MeSH terms

Adipocytes / metabolism*
Amino Acid Sequence / genetics
Binding Sites / physiology
Carrier Proteins / antagonists & inhibitors*
Carrier Proteins / genetics
Carrier Proteins / metabolism
Diabetes Mellitus, Type 2 / drug therapy*
Diabetes Mellitus, Type 2 / metabolism
Drug Delivery Systems / methods*
Fatty Acid-Binding Proteins
Fatty Acids / administration & dosage*
Fatty Acids / chemical synthesis*
Fatty Acids / metabolism
Humans
Molecular Sequence Data

Substances

Carrier Proteins
FABP5 protein, human
Fatty Acid-Binding Proteins
Fatty Acids