Adipocyte fatty acid binding protein (A-FABP/aP2) is a carrier protein expressed in both adipocytes and macrophages where it functions in intracellular fatty acid solubilization, trafficking, and metabolism. Molecular disruption of A-FABP/aP2 in mice results in improved insulin sensitivity and protection from atherosclerosis. HTS 01037 is a high-affinity ligand of adipocyte fatty acid binding protein (A-FABP/aP2) (Ki = 0.67 μM) that presumably competes with fatty acids for functional binding in the ligand-binding cavity of A-FABP/aP2. At a concentration of 10 μM, HTS 01037 antagonizes the protein-protein interaction of A-FABP/aP2 with hormone sensitive lipase in cultured C8PA lipocytes. HTS 01037 inhibits lipolysis in 3T3L1 adipocytes and reduces lipopolysaccharide-stimulated inflammation in bone marrow-derived macrophages, both effects of which are similar to the phenotype of A-FABP/aP2 knockout mice.
HTS 01037 is an inhibitor of fatty acid binding protein and a competitive antagonist of protein-protein interactions mediated by AFABP/aP2.
ChEBI: HTS 01037 is a ring assembly and a member of thiophenes.
1) Hertzel?et al. (2009),?Identification and characterization of a small molecule inhibitor of Fatty Acid binding proteins; J. Med. Chem,?52?6024
2) Long?et al. (2012),?Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner;?Biochim. Biophys. Acta,?1831?1199
3) Xu?et al.?(2015),?Uncoupling lipid metabolism from inflammation through fatty acid binding protein-dependent expression of USP2; Mol. Cell. Biol.,?35?1055
4) Steen?et al. (2016),?FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2; Mol. Cell. Biol.,?37 e00282
5) Boss?et al.?(2015),?FABP4 inhibition suppresses PPARgamma activity and VLDL-induced foam cell formation in IL-4-polarized human macrophages; Atherosclerosis,?240?424
