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.1 Molecular disruption of A-FABP/aP2 in mice results in improved insulin sensitivity and protection from atherosclerosis.2,3 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/aP2.4 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. 4 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.4
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2.Perrella, M.A., Pellacani, A., Layne, M.D., et al.Absence of adipocyte fatty acid binding protein prevents the development of accelerated atherosclerosis in hypercholesterolemic miceFASEB J.151774-1776(2001)
3.Furuhashi, M., Tuncman, G., G?rgün, C.Z., et al.Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2Nature447959-965(2007)
4.Hertzel, A.V., Hellberg, K., Reynolds, J.M., et al.Identification and characterization of a small molecule inhibitor of fatty acid binding proteinsJ. Med. Chem.526024-6031(2009)
