Uses
The Liver X Receptors (LXRα and LXRβ) are nuclear hormone receptors whose native ligands are oxysterols, such as 22(R)-hydroxycholesterol. The LXRs regulate the oxysterol-induced expression of cholesterol 7α-hydroxylase, the rate limiting enzyme of classic bile acid synthesis. T0901317 is a potent and selective agonist for both LXRα and LXRβ, with an EC50 of about 50 nM. T0901317 acting through LXR and in concert with its RXR heterodimerization partner induces the expression of the ABCA1 reverse cholesterol transporter. This acts to increase the efflux of cholesterol from enterocytes and thus inhibit the overall absorption of cholesterol.
Biological Activity
Potent, high affinity liver X receptor (LXR) agonist (EC 50 ~ 50 nM, Kd values are 7 and 22 nM for LXR- α and LRXR- β respectively). Upregulates expression of the ABCA1 gene associated with cholesterol efflux regulation and HDL metabolism. Decreases amyloid- β production in primary neurons in vitro . Displays an EC 50 of ~ 5 μ M for activation of bile acid farnesoid X receptors (FXRs); 10-fold more potent than natural FXR ligand chenodeoxycholic acid.
References
[1]. schultz j r, tu h, luk a, et al. role of lxrs in control of lipogenesis[j]. genes & development, 2000, 14(22): 2831-2838.
[2]. kumar n, solt l a, conkright j j, et al. the benzenesulfoamide t0901317 [n-(2, 2, 2-trifluoroethyl)-n-[4-[2, 2, 2-trifluoro-1-hydroxy-1-(trifluoromethyl) ethyl] phenyl]-benzenesulfonamide] is a novel retinoic acid receptor-related orphan receptor-α/γ inverse agonist[j]. molecular pharmacology, 2010, 77(2): 228-236.
[3]. houck k a, borchert k m, hepler c d, et al. t0901317 is a dual lxr/fxr agonist[j]. molecular genetics and metabolism, 2004, 83(1): 184-187.
[4]. liu y, yan c, wang y, et al. liver x receptor agonist t0901317 inhibition of glucocorticoid receptor expression in hepatocytes may contribute to the amelioration of diabetic syndrome in db/db mice[j]. endocrinology, 2006, 147(11): 5061-5068.
