Importance of the field: 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 glycaemic 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 in this review: Recent advances in the field of TGR5 modulators are reviewed, with a particular attention on patent applications and peer-reviewed publications in the past six years. Take home message: 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.
Patented TGR5 modulators: a review (2006 - present)
GIOIELLO, ANTIMO;NUTI, ROBERTO;MACCHIARULO, Antonio;PELLICCIARI, Roberto
2012
Abstract
Importance of the field: 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 glycaemic 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 in this review: Recent advances in the field of TGR5 modulators are reviewed, with a particular attention on patent applications and peer-reviewed publications in the past six years. Take home message: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
