Thiazolidinedione derivatives as novel GPR120 agonists for the treatment of type 2 diabetes

• Published in: RSC advances Vol. 12; no. 1; pp. 5732 - 5742
• Main Authors: Wang, Xuekun, Ji, Guoxia, Han, Xinyu, Hao, Huiran, Liu, Wenjing, Xue, Qidi, Guo, Qinghua, Wang, Shiben, Lei, Kang, Liu, Yadi
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 16.02.2022; The Royal Society of Chemistry
• Subjects: Chemistry; Diabetes; Fatty acids; Glucose; Insulin; Intestine; Selectivity
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d1ra08925k

GPR120, also called FFAR4, is preferentially expressed in the intestines, and can be stimulated by long-chain free fatty acids to increase the secretion of glucagon-like peptide-1 (GLP-1) from intestinal endocrine cells. It is known that GLP-1, as an incretin, can promote the insulin secretion from pancreatic cells in a glucose-dependent manner. Therefore, GPR120 is a potential drug target to treat type 2 diabetes. In this study, thiazolidinedione derivatives were found to be novel potent GPR120 agonists. Compound 5g , with excellent agonistic activity, selectivity, and metabolic stability, improved oral glucose tolerance in normal C57BL/6 mice in a dose-dependent manner. Moreover, compound 5g exhibited anti-diabetic activity by promoting insulin secretion in diet-induced obese mice. In summary, compound 5g might be a promising drug candidate for the treatment of type 2 diabetes. GPR120 has emerged as an attractive target for the treatment of type 2 diabetes and obesity. Thiazolidinedione derivatives were found to be novel potent GPR120 agonists.