未来药物法尼醇X受体激动剂奥贝胆酸.PDFVIP

·396 · 现代药物与临床 Drugs Clinic 第 31 卷 第 3 期 2016 年 3 月 • 未来药物 • 法尼醇 X 受体激动剂奥贝胆酸 1, 2 1 3 1* 1* 朱世超 ，郑学敏 ，张 玥 ，刘 巍 ，周植星 1. 天津药物研究院 天津市新药设计与发现重点实验室，天津 300193 2. 天津医科大学，天津 300070 3. 天津中医药大学，天津 300193 摘 要：奥贝胆酸是一种治疗原发性胆汁性肝硬化和非酒精性脂肪肝的新型候选药物，由美国 Intercept 制药公司研发，其 机制主要是通过激动法尼醇 X 受体，调节相关基因，影响胆汁酸的合成、分泌、转运和吸收。临床研究表明，对熊去氧胆 酸不能完全耐受的患者，通过服用奥贝胆酸能够明显改善碱性磷酸酶和血清胆红素的水平，提示奥贝胆酸的临床效果可能优 于现有药物熊去氧胆酸。将从奥贝胆酸的药物概况、相关背景、合成路线、药理作用、临床前及临床试验研究以及安全性评 价方面进行简述。 关键词：奥贝胆酸；熊去氧胆酸；原发性胆汁性肝硬化；非酒精性脂肪肝 中图分类号：R975 文献标志码：A 文章编号：1674 - 5515(2016)03 - 0396 - 05 DOI: 10.7501/j.issn.1674-5515.2016.03.030 A farnesoid X receptor agonist: obeticholic acid 1, 2 1 3 1 1 ZHU Shi-chao , ZHENG Xue-min , ZHANG Yue , LIU Wei , ZHOU Zhi-xing 1. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China 2. Tianjin Medical University, Tianjin 300070, China 3. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China Abstract: Obeticholic acid is a drug candidate for the treatment of primary biliary cirrhosis and nonalcoholic fatty liver disease, which was developed by Intercept Pharmaceuticals. It mainly regulates related gene and affects the synthesis, secretion, transport, and absorption of bile acid through activating farnesoid X receptor. Clinical studies have shown that obeticholic acid can improve the level of alkaline phosphatase and serum bilirubin to the subjects who cannot inadequate response to ursodeoxycholic acid therapy, so obeticholic acid may be prior to ursodeoxycholic acid.