Biomolecules & Therapeutics

  • 제22권5호
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  • Pages.400-405
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  • 2014
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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DOI QR Code

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies

  • Kim, SoRa (New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center) ;
  • Kim, Dae Hoon (New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center) ;
  • Kim, Young-Seok (New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center) ;
  • Ha, Tae-Young (New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center) ;
  • Yang, Jin (New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center) ;
  • Park, Soo Hyun (Bio-therapy Human Resources Center, Animal Medical Center and Department of Veterinary Physiology, College of Veterrinary Medicine, Chonnam National University) ;
  • Jeong, Kwang Won (College of Pharmacy, Gachon University) ;
  • Rhee, Jae-Keol (New Drug Discovery Lab., Hyundai Pharmaceutical Co. Ltd., Gyeong-Gi Bio-Center)
  • 투고 : 2014.03.20
  • 심사 : 2014.06.13
  • 발행 : 2014.09.30
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초록

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 b-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.

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참고문헌

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피인용 문헌

  1. Therapeutic application of GPR119 ligands in metabolic disorders 2017, https://doi.org/10.1111/dom.13062
  2. Structure and biological activity of endogenous and synthetic agonists of GPR119 vol.87, pp.2, 2018, https://doi.org/10.1070/rcr4737
  3. Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease vol.26, pp.1, 2021, https://doi.org/10.1186/s11658-021-00276-7