Patented TGR5 modulators: a review (2006 - present)

Expert Opin Ther Pat. 2012 Dec;22(12):1399-414. doi: 10.1517/13543776.2012.733000. Epub 2012 Oct 6.


Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy
  • Atherosclerosis / metabolism
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cardiovascular Agents / chemistry
  • Cardiovascular Agents / pharmacology*
  • Cardiovascular Agents / therapeutic use
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / physiopathology
  • Drug Design*
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Insulin Resistance
  • Ligands
  • Molecular Structure
  • Patents as Topic*
  • Protein Conformation
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Structure-Activity Relationship


  • Blood Glucose
  • Cardiovascular Agents
  • GPBAR1 protein, human
  • Hypoglycemic Agents
  • Insulin
  • Ligands
  • Receptors, G-Protein-Coupled