The farnesoid X receptor: a novel drug target?
Bile acids are end products of cholesterol metabolism. They are exclusively synthesised by the liver and subsequently secreted via the bile duct into the intestine to facilitate the absorption of dietary fat and fat-soluble vitamins. Nuclear receptors are ligand-activated transcription factors. The farnesoid X receptor (FXR) has recently been identified as a bile acid-activated nuclear receptor. FXR controls bile-acid synthesis, conjugation and transport, as well as lipid metabolism. Recent advances in FXR biology demonstrate that FXR may represent a valuable target for the identification of novel drugs to treat dyslipidaemia and cholestasis. However, for therapeutic purposes the development of selective FXR modulators, which only activate or inhibit specific FXR target genes and as such induce specific responses, will be required.
Claudel
Thierry
T
Unité de Recherche 545, Institut National de la Santé et de la Recherche Médicale, Département d'Athérosclérose, Institut Pasteur de Lille and the Faculté de Pharmacie, Université de Lille II, Lille, France.
Sturm
Ekkehard
E
Kuipers
Folkert
F
Staels
Bart
B
D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D002210:Caprylates / Q000737:chemistry / Q000494:pharmacology; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002779:Cholestasis / Q000188:drug therapy; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000737:chemistry; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000737:chemistry / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors / Q000819:agonists* / Q000737:chemistry; D000099150:Receptor, Farnesoid X-Activated
D001555:Benzene Derivatives; D002210:Caprylates; D002635:Chenodeoxycholic Acid; D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; D010647:Phenyl Ethers; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C472778:AGN 34 compound; C474615:fexaramine; C464660:obeticholic acid