GSK-2033

Description: GSK2033 is a novel, potent and cell-active LXR (liver X receptor) antagonist with pIC50s of 7 and 7.4 for LXRalpha or LXRbeta. It enhances T-cell proliferation and blocks T 0901317-antiproliferative activity on T-cells and is cell permeable. GSK2033 displays systemic exposure. Although GSK2033 performed as expected in cell-based models as a LXR inverse agonist, it displayed unexpected activity in the mouse NAFLD model. The expression of lipogenic enzyme genes such as fatty acid synthase and sterol regulatory binding protein 1c were induced rather than suppressed and no effect on hepatic steatosis was found. Further characterization of the specificity of GSK2033 revealed that it displayed a significant degree of promiscuity, targeting a number of other nuclear receptors that could clearly alter hepatic gene expression.

References: J Med Chem. 2010 Apr 22; 53(8):3412-6; Biochem Biophys Res Commun. 2016 Oct 21; 479(3):424-428.