调节胆汁酸途径和 TGR5 受体治疗肝脏和胃肠道疾病。
Modulating bile acid pathways and TGR5 receptors for treating liver and GI diseases.
机构信息
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
出版信息
Curr Opin Pharmacol. 2017 Dec;37:80-86. doi: 10.1016/j.coph.2017.09.008. Epub 2017 Nov 5.
Abstract
Bile acids are central signals in enterohepatic communication and also integrate microbiota-derived signals into this signaling axis. Discovery of the tissue distribution and signaling pathways activated by the natural receptors for bile acids, farnesoid X receptor and G protein-coupled bile acid receptor 1 (GPBAR1) also known as TGR5, and bile acid transporters has led to the development of therapeutic agents that target these molecules. Obeticholic acid, a selective FXR agonist, and NGM282, a non-mitogenic FGF-19 analog, are two of the agents in this pipeline. Obeticholic acid has been approved by regulatory agencies for use in patients with primary biliary cholangitis.
摘要
胆汁酸是肠肝通讯的核心信号，也将微生物群衍生的信号整合到这个信号轴中。天然胆汁酸受体法尼酯 X 受体和 G 蛋白偶联胆汁酸受体 1（也称为 TGR5）以及胆汁酸转运蛋白的组织分布和信号通路的发现，导致了针对这些分子的治疗药物的发展。奥贝胆酸是一种选择性 FXR 激动剂，而 NGM282 是一种非有丝分裂 FGF-19 类似物，是该领域的两种药物。奥贝胆酸已被监管机构批准用于原发性胆汁性胆管炎患者。
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