G-protein coupled receptor 119 (GPR119) expression in pancreatic β-cells and intestinal L cells is a potential therapeutic target for treating type 2 diabetes.
Here, we report that compound II-18 with its excellent agonistic activity and its orally effective activity in decreasing blood glucose deviations may serve as a potent GPR119 agonist for the treatment of T2DM.
The fourteen novel compounds thus synthesized were tested for ability to target GPR119, a G-protein coupled target receptor that plays critical role in regulation of type-2 diabetes mellitus.
Since GPR119 receptor activation ameliorates Type 2 Diabetes through an increase in glucose-dependent insulin release, the development of new GPR119 receptor agonists would be worthwhile.
Efficacy and safety of the G protein-coupled receptor 119 agonist DS-8500a in Japanese type 2 diabetes mellitus patients with inadequate glycemic control on sitagliptin: A phase 2 randomized placebo-controlled study.
GPR119 drug discovery efforts in the pharmaceutical industry for the treatment of type 2 diabetes mellitus (T2DM) and obesity, were initiated based on its restricted distribution in pancreas and GI tract, and its possible role in glucose homeostasis.
Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes.
A class of novel pyrimidine derivatives bearing diverse conformationally restricted azabicyclic ether/amine were designed, synthesized and evaluated for their GPR119 agonist activities against type 2 diabetes.
Due to this dual mechanism of action, the development of small molecule GPR119 agonists has received much interest for the treatment of type 2 diabetes.
These findings demonstrate that β-cell GPR119 expression is dispensable for the physiological control of insulin secretion and the pharmacological response to GPR119 agonism, findings that may inform the lack of robust efficacy in clinical programs assessing GPR119 agonists for the therapy of type 2 diabetes.
Here, we identified a novel structural class of small-molecule GPR119 agonists, HD0471042, consisting of substituted a 3-isopropyl-1,2,4-oxadiazol-piperidine derivative with promising potential for the treatment of T2DM.