双数激素受体（farnesoid X receptor，FXR）是受胆汁酸（bile acid，BA）激活的核受体，高表达于肝脏和肠道，调控胆固醇和胆汁酸代谢、肝葡萄糖生成、脂肪生成、炎症和纤维化相关基因的表达，此外还控制肠道屏障完整性，阻止细菌跨位置，并维持肠道菌群的平衡。非酒精性脂肪性肝病（non-alcoholic steatohepatitis，NASH）是非酒精性脂肪肝病（non-alcoholic fatty liver disease，NAFLD）的晚期阶段，其特征为肝脂肪变性、肝细胞损伤（肿胀）和炎症，从而导致纤维化、肝硬化和肝细胞癌。NASH是一个重要的医学需求，但目前尚无药物治疗获得批准。NASH发展中出现的多效机制提供了多种治疗机会，其中FXR激活已成为一个已确立的药物靶点。各种FXR激动剂具有不同的理化性质，可以广义上分为胆汁酸衍生物、非胆汁酸类固醇型FXR激动剂、非类固醇类FXR激动剂和部分FXR激动剂，并且在临床开发中处于先进阶段。在本综述中，我们将总结最先进的FXR激动剂的关键临床前和临床特征，并对其在NASH治疗中的潜力进行评价。版权所有 © 2023. Elsevier B.V. 出版。

The farnesoid X receptor (FXR), a bile acid (BA)-activated nuclear receptor highly expressed in liver and intestine, regulates the expression of genes involved in cholesterol and bile acid homeostasis, hepatic gluconeogenesis, lipogenesis, inflammation and fibrosis, in addition to controlling the intestinal barrier integrity, preventing bacterial translocation and maintaining the gut microbiota eubiosis. Non-alcoholic steatohepatitis (NASH), an advanced stage of non-alcoholic fatty liver disease (NAFLD), is characterized by hepatic steatosis, hepatocyte damage (ballooning) and inflammation, leading to fibrosis, liver cirrhosis and hepatocellular carcinoma. NASH represents a major unmet medical need, but no pharmacological treatments have yet been approved. The pleiotropic mechanisms involved in NASH development offer a range of therapeutic opportunities and among them FXR activation has emerged as an established pharmacological target. Various FXR agonists with different physicochemical properties, which can be broadly classified as BA derivatives, non-BA-derived steroidal FXR agonists, non-steroidal FXR agonists, and partial FXR agonists, are in advanced clinical development. In this review we will summarize key preclinical and clinical features of the most advanced FXR agonists and critically evaluate their potential in NASH treatment.Copyright © 2023. Published by Elsevier B.V.