发现一种用于治疗原发性胆汁性肝硬化的新型选择性双过氧化物酶体增殖物激活受体α/δ激动剂。
Discovery of a Novel Selective Dual Peroxisome Proliferator-Activated Receptor α/δ Agonist for the Treatment of Primary Biliary Cirrhosis.
作者信息
Jiang Zhigan, Liu Xing, Yuan Zhiliang, He Haiying, Wang Jing, Zhang Xiao, Gong Zhen, Hou Lijuan, Shen Liang, Guo Fengxun, Zhang Jiliang, Wang Jianhua, Xu Deming, Liu Zhuowei, Li Haijun, Chen Xiaoxin, Long Chaofeng, Li Jian, Chen Shuhui
机构信息
WuXi AppTec (Shanghai) Co., Ltd, 288 FuTe Zhong Road, Shanghai 200131, P. R. China.
R&D Center, Guangdong Zhongsheng Pharmaceutical Co., Ltd. The Information Area of Xihu Industrial Base, Shilong Town, Dongguan, Guangdong Province 523325, P. R. China.
出版信息
ACS Med Chem Lett. 2019 Jun 24;10(7):1068-1073. doi: 10.1021/acsmedchemlett.9b00189. eCollection 2019 Jul 11.
Abstract
A novel peroxisome proliferator-activated receptor (PPAR) α/δ dual agonist was developed with an EC of 8 nM for PPARα, 5 nM for PPARδ, and >300-fold selectivity against PPARγ (EC = 2939 nM), respectively. Further ADME and pharmacokinetic studies indicated possessed distinguished and profiles. The excellent efficacy of compound was demonstrated by the rat primary biliary cirrhosis (PBC) model.
摘要
一种新型过氧化物酶体增殖物激活受体（PPAR）α/δ双重激动剂被研发出来，其对PPARα的半数有效浓度（EC）为8 nM，对PPARδ的EC为5 nM，对PPARγ（EC = 2939 nM）的选择性大于300倍。进一步的药物代谢动力学和药代动力学研究表明其具有独特的性质和特征。该化合物在大鼠原发性胆汁性肝硬化（PBC）模型中显示出优异的疗效。
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