Intercept Pharmaceuticals, 18 Desbrosses Street, New York, NY 10013, USA.
Drug Discov Today. 2012 Sep;17(17-18):988-97. doi: 10.1016/j.drudis.2012.05.012. Epub 2012 May 29.
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition evolving in a proportion of patients into nonalcoholic steatohepatitis (NASH), an aggressive form of NAFLD associated with increased cardiovascular mortality and significant risk of progressive liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma. At present, no specific therapies for NASH exist. In this review, we examine the evidence supporting activation of the farnesoid X receptor (FXR), a nuclear hormone receptor regulated by bile acids (BAs), for the treatment of NASH. We also discuss the potential of the semi-synthetic BA derivative obeticholic acid (OCA), a first-in-class FXR agonist, as a safe and effective drug to address this significant unmet medical need.
非酒精性脂肪性肝病 (NAFLD) 是一种高发的慢性肝脏疾病，一部分患者会进展为非酒精性脂肪性肝炎 (NASH)，这是一种侵袭性的 NAFLD 形式，与心血管死亡率增加和进行性肝脏疾病（包括纤维化、肝硬化和肝细胞癌）的显著风险相关。目前，尚无针对 NASH 的特异性治疗方法。在这篇综述中，我们研究了支持激活法尼醇 X 受体 (FXR) 的证据，FXR 是一种受胆汁酸 (BAs) 调节的核激素受体，用于治疗 NASH。我们还讨论了半合成 BA 衍生物奥贝胆酸 (OCA) 的潜力，OCA 是一种首创的 FXR 激动剂，作为一种安全有效的药物，可以满足这一重大未满足的医疗需求。
