title: HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies.
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 β-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic β-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.
authors.affiliation: New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270.
authors.forename: SoRa
authors.initials: S
authors.lastname: Kim
authors.affiliation: New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270 ; Bio-therapy Human Resources Center, Animal Medical Center and Department of Veterinary Physiology, College of Veterrinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: Dae Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270.
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Kim
authors.affiliation: New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Ha
authors.affiliation: New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Bio-therapy Human Resources Center, Animal Medical Center and Department of Veterinary Physiology, College of Veterrinary Medicine, Chonnam National University, Gwangju 500-757.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Kwang Won
authors.initials: KW
authors.lastname: Jeong
authors.affiliation: New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center, Suwon 443-270.
authors.forename: Jae-Keol
authors.initials: JK
authors.lastname: Rhee
keywords: GLP-1; GPR119 agonist; Type 2 diabetes