E17110 promotes reverse cholesterol transport with liver X receptor β agonist activity in vitro.

Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound. E17110 was identified as a novel LXRβ agonist by using a cell-based screening method. E17110 could increase the expression of ABCA1 and ABCG1 in RAW264.7 macrophages and significantly reduce cellular lipid accumulation and promote cholesterol efflux. Interestingly, we found that LXRβ had distinct interactions with E17110 compared to TO901317.

肝X受体（LXR）在胆固醇逆向转运（RCT）中起重要作用，LXR的激活可减少动脉粥样硬化。在本研究中，我们使用基于细胞的筛选方法来鉴定新的潜在LXRβ激动剂。一种具有LXRβ激动剂活性的新型苯并呋喃 - 2 - 羧酸酯衍生物被鉴定出来：E17110对LXRβ有显著的激活作用，半数有效浓度（EC50）值为0.72 μmol/L。E17110还增加了RAW264.7巨噬细胞中ATP结合盒转运体A1（ABCA1）和G1（ABCG1）的表达。此外，E17110显著减少了RAW264.7巨噬细胞中的细胞脂质积累并促进了胆固醇外流。有趣的是，我们发现与TO901317相比，LXRβ配体结合域中的关键氨基酸与E17110有不同的相互作用。这些结果表明，通过筛选，E17110在体外被鉴定为一种具有LXRβ激动剂活性的新型化合物，并可被开发为一种潜在的抗动脉粥样硬化先导化合物。 通过基于细胞的筛选方法，E17110被鉴定为一种新型的LXRβ激动剂。E17110可增加RAW264.7巨噬细胞中ABCA1和ABCG1的表达，并显著减少细胞脂质积累和促进胆固醇外流。有趣的是，我们发现与TO901317相比，LXRβ与E17110有不同的相互作用。