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

作     者：Ni Li Xiao Wang Peng Liu Duo Lu Wei Jiang Yanni Xu Shuyi Si 

作者机构：State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2016年第6卷第3期

页      面：198-204页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100706[医学-药理学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.81273515,81321004 and 81503065) the Key New Drug Creation and Manufacturing Program(Nos.2012ZX09301002-003 and 2012ZX09301002-001) the Basic Scientific Research Program of Materia Medica,CAMS(2014ZD03) 

主　　题：LXRβ Atherosclerosis ABCA1 ABCG1 Reverse cholesterol transport Cholesterol efflux 

摘      要：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.