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Overview
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Background
XL335 is a potent, selective and orally bioavailable agonist of the farnesoid X receptor (FXR) with EC50 value of 4 nM [1].XL335 has shown to reduce IL-6-induced both mRNA and protein expression of CRP via FXR in human hepatoma Hep3B cells. XL335 remarkably reduced LPS-induced SAP and SAA3 mRNA expression in WT mice, but not in FXR/KO mice [2]. Additionally, in hepatoma cells, XL335 block the lipid accumulation induced by palmitic acid (PA). In vivo, XL335 has shown to decrease portal vein endotoxin level and reduce inflammation induced by fructose in mice. XL335 attenuated inflammation and suppressed ADRP expression in lipopolysaccharide (LPS)-induced mice [3].
[1] Flatt B1, Martin R, Wang TL, Mahaney P, Murphy B, Gu XH, Foster P, Li J, Pircher P, Petrowski M, Schulman I, Westin S, Wrobel J, Yan G, Bischoff E, Daige C,Mohan R. Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR). J Med Chem. 2009 Feb 26;52(4):904-7. doi: 10.1021/jm8014124.
[2] Zhang S1, Liu Q, Wang J, Harnish DC. Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists. Biochem Biophys Res Commun. 2009 Feb 6;379(2):476-9.
[3] Liu X1, Xue R2, Ji L1, Zhang X1, Wu J3, Gu J1, Zhou M4, Chen S5. Activation of farnesoid X receptor (FXR) protects against fructose-induced liver steatosis via inflammatory inhibition and ADRP reduction. Biochem Biophys Res Commun. 2014 Jul 18;450(1):117-23.
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