Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target.
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.
Lehmann
Fredik
F
Department of Medicinal Chemistry, Biovitrum AB, SE-751 37 Uppsala, Sweden.
Haile
Saba
S
Axen
Eva
E
Medina
Carmen
C
Uppenberg
Jonas
J
Svensson
Stefan
S
Lundbäck
Thomas
T
Rondahl
Lena
L
Barf
Tjeerd
T
D017667:Adipocytes / Q000378:metabolism*; D000595:Amino Acid Sequence / Q000235:genetics; D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data
D002352:Carrier Proteins; C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids