title: Patented TGR5 modulators: a review (2006 - present).
abstract: BACKGROUND
  The G protein-coupled receptor TGR5 is a key player of the bile acid signaling network, and its activation has been proved to increase the glycemic control, to enhance energy expenditure and to exert anti-inflammatory actions. Accordingly, TGR5 ligands have emerged in drug discovery and preclinical appraisals as promising agents for the treatment of liver diseases, metabolic syndrome and related disorders.
  
  
  METHODS
  Recent advances in the field of TGR5 modulators are reviewed, with a particular attention on patent applications and peer-reviewed publications in the past 6 years.
  
  
  CONCLUSIONS
  Activation of TGR5 showed to protect mice from diabesity and insulin resistance, to improve liver functions, as well as to attenuate the development of atherosclerosis. However, although the efficacy of TGR5 agonists in mice is encouraging, further studies are needed to determine their potential in humans and to evaluate carefully the balance between the therapeutic benefits and adverse effects associated with the target. The development of new TGR5 selective ligands to support studies in animal models will surely facilitate the understanding of the complexity of TGR5 signaling network.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy. antimo@chimfarm.unipg.it
authors.forename: Antimo
authors.initials: A
authors.lastname: Gioiello
authors.forename: Emiliano
authors.initials: E
authors.lastname: Rosatelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Nuti
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008024:Ligands; D015394:Molecular Structure; D010330:Patents as Topic; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D002317:Cardiovascular Agents; C473772:GPBAR1 protein, human; D007004:Hypoglycemic Agents; D007328:Insulin; D008024:Ligands; D043562:Receptors, G-Protein-Coupled