title: Bile acid receptors as targets for drug development.
abstract: The intracellular nuclear receptor farnesoid X receptor and the transmembrane G protein-coupled receptor TGR5 respond to bile acids by activating transcriptional networks and/or signalling cascades. These cascades affect the expression of a great number of target genes relevant for bile acid, cholesterol, lipid and carbohydrate metabolism, as well as genes involved in inflammation, fibrosis and carcinogenesis. Pregnane X receptor, vitamin D receptor and constitutive androstane receptor are additional nuclear receptors that respond to bile acids, albeit to a more restricted set of species of bile acids. Recognition of dedicated bile acid receptors prompted the development of semi-synthetic bile acid analogues and nonsteroidal compounds that target these receptors. These agents hold promise to become a new class of drugs for the treatment of chronic liver disease, hepatocellular cancer and extrahepatic inflammatory and metabolic diseases. This Review discusses the relevant bile acid receptors, the new drugs that target bile acid signalling and their possible applications.
authors: Department of Surgery, NUTRIM School of Nutrition, Toxicology and Metabolism, Maastricht University, PO Box 616, 6200 MD, Maastricht, Netherlands.
authors: Frank G
authors: FG
authors: Schaap
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors: Michael
authors: M
authors: Trauner
authors: Department of Gastroenterology and Hepatology, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.
authors: Peter L M
authors: PL
authors: Jansen
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D004195:Disease Models, Animal; D004358:Drug Therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008107:Liver Diseases / Q000188:drug therapy*; D008113:Liver Neoplasms / Q000188:drug therapy; D008659:Metabolic Diseases / Q000188:drug therapy*; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear