HTS01037 (682741-29-3) inhibits fatty acid binding proteins. Inhibits lipolysis in 3T3-L1 adipocytes and reduces LPS-stimulated inflammation in cultured macrophages. Acts as an antagonist of the protein-protein interaction between AFABP/aP2 and hormone sensitive lipase but does not activate PPARg in macrophages1. Inhibits FABP-dependent and fatty acid-stimulated leukotriene C4 biosynthesis2. Reduces intracellular free fatty acid levels, lowering macrophage inflammation and ER stress3. Reduces LPS-stimulated IL-1b secretion in a mouse model4. Inhibits VLDL-induced foam cell formation5.
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., Epub ahead of print, Oct. 17
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