ZLY28

ZLY28 is a farnesoid X receptor (FXR) agonist and an inhibitor of fatty acid binding protein 1 (FABP1).¹ It selectively induces reporter gene expression in HepG2 cells expressing human FXR (EC₅₀ = 143 nM) over cells expressing 19 other receptors (EC₅₀s = >10,000 nM for all). ZLY28 selectively inhibits FABP1 (IC₅₀ = 2.7 µM) over FABP3 (IC₅₀ = >30 µM) but also inhibits FABP4 (IC₅₀ = 6.3 µM). In vivo, ZLY28 (20 mg/kg) induces FXR-related gene expression in the ileum but not the liver in a mouse model of carbon tetrachloride-induced non-alcoholic steatohepatitis (NASH). It also reduces hepatocyte ballooning, as well as hepatic lobular inflammation and steatosis in the same model.