HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies.
10.4062/biomolther.2014.035
- Author:
Sora KIM
1
;
Dae Hoon KIM
;
Young Seok KIM
;
Tae Young HA
;
Jin YANG
;
Soo Hyun PARK
;
Kwang Won JEONG
;
Jae Keol RHEE
Author Information
1. New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270, Republic of Korea. 20090024@hdpharm.co.kr, 20100083@hdpharm.co.kr
- Publication Type:Original Article
- Keywords:
GPR119 agonist;
Type 2 diabetes;
GLP-1
- MeSH:
Animals;
Blood Glucose;
Diabetes Mellitus, Type 2;
Glucagon-Like Peptide 1;
Glucose Tolerance Test;
GTP-Binding Proteins;
Humans;
Insulin;
Mice;
Plasma;
Rodentia
- From:Biomolecules & Therapeutics
2014;22(5):400-405
- CountryRepublic of Korea
- Language:English
-
Abstract:
G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic beta-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic beta-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.
