Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Expert Opin Ther Pat. 2012 Dec;22(12):1399-414. doi: 10.1517/13543776.2012.733000. Epub 2012 Oct 6.
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.
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.
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.
G 蛋白偶联受体 TGR5 是胆汁酸信号网络的关键参与者，其激活已被证明可以提高血糖控制水平，增加能量消耗并发挥抗炎作用。因此，TGR5 配体在药物发现和临床前评估中作为治疗肝脏疾病、代谢综合征和相关疾病的有前途的药物出现。
本文综述了 TGR5 调节剂领域的最新进展，特别关注过去 6 年的专利申请和同行评议出版物。
TGR5 的激活已被证明可以保护小鼠免受糖尿病和胰岛素抵抗的影响，改善肝功能，并减轻动脉粥样硬化的发展。然而，尽管 TGR5 激动剂在小鼠中的疗效令人鼓舞，但仍需要进一步的研究来确定它们在人类中的潜在应用，并仔细评估与该靶点相关的治疗益处和不良反应之间的平衡。开发新的 TGR5 选择性配体将有助于支持动物模型中的研究，从而促进对 TGR5 信号网络复杂性的理解。
