SR9243, an LXR inverse agonist, can induce LXR-corepressor interaction; shows anticancer activity and selectively targets the lipogenesis and Warburg effect.

在表达LXRs的HEK293细胞中，SR9243通过增强LXR-核抑制因子的招募来抑制LXR的激活。在多种癌细胞类型中，SR9243降低癌细胞活性，诱导凋亡细胞死亡，并使癌细胞对化疗治疗更加敏感。[1]

在Ob/Ob小鼠中，当它们摄入高脂饮食时，SR9243（60 mg/kg, i.p.）抑制了LXR依赖的脂肪生成酶基因表达和肿瘤生长。[1]

ALK5 Fluorescence Polarization Binding Assay: GW788388 binding to ALK5 is tested on purified recombinant GST?ALK5 (residues 198-503). Displacement of rhodamine green fluorescently labeled ATP competitive inhibitor by different concentrations of GW788388 is used to calculate a binding pIC50. GST?ALK5 is added to a buffer containing 62.5 mM N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (Hepes), pH 7.5, 1 mM dithiothreitol (DTT), 12.5 mM MgCl2, 1.25 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and 1 nM rhodamine green-labeled ligand so that the final ALK5 concentration is 10 nM based on active-site titration of the enzyme. The enzyme/ligand reagent (40 μL) is added to 384-well assay plates containing 1 μL of different concentrations of GW788388. The plates are read immediately on a LJL Acquest fluorescence reader with excitation, emission, and dichroic filters of 485, 530, and 505 nm, respectively. The fluorescence polarization for each well is calculated by the Acquest and is then imported into curve-fitting software for construction of concentration?response curves.

Cells are cultured in 96 well plates and treated with designated amounts of SR9243 for 96 hr in media containing 1% FBS and antibiotics. Cell-viability is assessed using the Cell-titre 96 kit according to the manufacturer's guidelines. Cell culture media is supplemented with oleate, stearate and palmitate dissolved in methanol to a concentration of 25 mM. 25 mM stocks are then diluted 10 fold in PBS containing 0.9% BSA. Lipid stocks (100X) are stored at ?20° until needed.(Only for Reference)