title: In vivo efficacy of HD0471953: a novel GPR119 agonist for the treatment of type 2 diabetes mellitus.
abstract: G-protein coupled receptor 119 (GPR119) has emerged as a promising new target for the treatment of type 2 diabetes mellitus. The expression of GPR119 on the pancreatic B cells and intestinal L cells provides a unique opportunity for a single drug to promote insulin and GLP-1 secretion. In this study, we identified a novel small molecule GPR119 agonist, HD0471953, from our large library of synthetic compounds based on its ability to anti-hyperglycemic effects on T2DM murine models. We have tested the acute efficacy of HD0471953 by the oral glucose tolerance test (OGTT) with normal C57BL/6J mice. Then, chronic administrations of HD0471953 were performed to evaluate the efficacy on various diabetic rodent models. Single administration of HD0471953 showed improved glycemic control with a dose-dependent manner in OGTT with normal mice, and the insulin and GLP-1 were also increased. To identify chronic efficacy, we have observed a decline of blood glucose and fasting insulin in a dose-dependent manner of 10, 20, and 50 mpk in db/db mice. The results suggest that HD0471953 may be a potentially promising anti-hyperglycemic agent for the treatment of patients with type 2 diabetes mellitus.
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea ; College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Seoul 135-545, Republic of Korea.
authors.forename: Dae-Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Seoul 135-545, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea.
authors.forename: Chun Hwa
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Ha
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Hyundai Pharmaceutical Co. Ltd., 204-4 Nonhyeon 1-dong, Gangnam-gu, Seoul 135-545, Republic of Korea.
authors.forename: Jae-Keol
authors.initials: JK
authors.lastname: Rhee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; C516207:Gpr119 protein, mouse; D007004:Hypoglycemic Agents; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP