GSK2033 is an antagonist of liver X receptor α (LXRα) and LXRβ (IC50s = 0.1 and 0.398 ?M, respectively) that has no agonist activity in an LXR transactivation assay.1 It inhibits LXR agonist-induced and basal expression of the LXR target genes ATP-binding cassette transporter 1 (ABCA1) and sterol regulatory element binding protein 1c (SREBP-1c) in THP-1 and HepG2 cells, respectively. However, GSK2033 binds promiscuously to a variety of nuclear receptors including RORγ, RXRα, ERα, and ERβ in a nuclear receptor specificity assay in HEK293 cells and, in a mouse model of non-alcoholic fatty liver disease (NAFLD), it induces the expression of fatty acid synthase and SREBP-1.2
1.Zuercher, W.J., Buckholz, R.G., Campobasso, N., et al.Discovery of tertiary sulfonamides as potent liver X receptor antagonistsJ. Med. Chem.53(8)3412-3416(2010) 2.Griffett, K., and Burris, T.P.Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver diseaseBiochem. Biophys. Res. Commun.479(3)424-428(2016)