法尼醇X受体激动剂奥贝胆酸

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。

A farnesoid X receptor agonist: obeticholic acid

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. This paper mainly discusses the drug situation, background, route of synthesis, pharmacological action, preclinical, clinical trials research, and safety evaluation.