The liver X receptors (LXRs) are nuclear receptors that act as ligand-dependent transcription factors.¹ They modulate lipid, cholesterol, and carbohydrate metabolism and homeostasis. SR9238 is an inverse agonist of the two LXR isoforms, LXRα and LXRβ (IC₅₀s = 214 and 43 nM, respectively).² It displays liver specificity in vivo, with little action at peripheral LXR. SR9238 suppresses hepatic lipogenesis, inflammation, lipid accumulation, and fibrosis in mouse models of non-alcoholic steatohepatitis.^2,3 It also reduces plasma cholesterol levels in diet-induced obese mice.²

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1.Gabbi, C.,Warner, M. and Gustafsson, J.Ä. Action mechanisms of liver X receptors. Biochemical and Biophysical Research Communications 446(3), 647-650 (2014).

2.Griffett, K.,Solt, L.A.,El-Dien, B., et al. A liver-selective LXR inverse agonist that suppresses hepatic steatosis. ACS Chemical Biology 8(3), 559-567 (2013).

3.Griffett, K.,Welch, R.D.,Flaveny, C.A., et al. The LXR inverse agonist SR9238 suppresses fibrosis in a model of non-alcoholic steatohepatitis. Mol.Metab. 4(4), 353-357 (2015).