Abstract
Glucagon-like peptide-1 (GLP-1) is the main member of the incretin family and stimulates insulin secretion by binding with its specific receptor on pancreatic β-cells. In addition, GLP-1 exerts broad beneficial effects on the glucose regulation by suppressing food intake and delaying stomach emptying. Now, long acting GLP-1 analogs including exenatide and liraglutide have been approved for the treatment of diabetes mellitus type 2, however long-term injection can limit their use for these chronic patients. In this report, the authors provide a review on the development of non-peptide GLP-1 receptor agonists and introduce a novel agonist DA-15864.
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Abu-Hamdah, R., Rabiee, A., Meneilly, G. S., Shannon, R. P., Andersen, D. K., and Elahi, D., The extrapancreatic effects of glucagon-like peptide-1 and related peptides. J. Clin. Endocrinol. Metab., 94, 1843–1852 (2009).
Baggio, L. L. and Drucker, D. J., Biology of incretins: GLP-1 and GIP. Gastroenterology, 132, 2131–2157 (2007).
Chen, D., Liao, J., Li, N., Zhou, C., Liu, Q., Wang, G., Zhang, R., Zhang, S., Lin, L., Chen, K., Xie, X., Nan, F., Young, A. A., and Wang, M. W., A nonpeptidic agonist of glucagonlike peptide 1 receptors with efficacy in diabetic db/db mice. Proc. Natl. Acad. Sci. U. S. A., 104, 943–948 (2007).
Dong, M., Gao, M., Pinon, D. I., and Miker, L. J., Insights into the structural basis of endogenous agonist activation of family B G protein-coupled receptors. Mol. Endocrinol., 22, 1489–1499 (2008).
Hoare, S. R. J., Mechanisms of peptide and nonpeptide ligand binding to class B G-protein-coupled receptors. Drug Discov. Today, 10, 417–427 (2005).
Kim, M. K., Kim, H. D., Cheong, Y. H., Yang, E. K., Choi, S. H., Shin, C. Y., Jung, H. H., Kim, E. J., Moon, H. S., Yang, H. S., and Son, M. H., Orally active small molecule GLP-1R agonist, DA-15864 increases insulin secretion in mice. 70 th Scientific Sessions of Annual Meeting of American Diabetes Association, Jun 25–29, 2010, Orlando, FL; Poster presentation (590-P).
Knudsen, L. B., Kiel, D., Teng, M., Behrens, C., Bhumralkar, D., Kodra, J. T., Holst, J. J., Jeppesen, C. B., Johnson, M., D., de Jong, J. C., Jorgensen, A. S., Kercher, T., Kostrowicki, J., Madsen, P., Olesen, P. H., Petersen, J. S., Poulsen, F., Sidelmann, U. G., Sturis, J., Truesdale, L., May, J., and Lau, J., Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc. Natl. Acad. Sci. U. S. A., 104, 937–942 (2007).
Kwon, D. Y., Kim, Y. S., Ahn, I. S., Kim, D. S., Kang, S., Hong, S. M., and Park, S. M., Exendin-4 potentiates insulinotropic action partly via increasing β-cell proliferation and neogenesis and decreasing apoptosis in association with the attenuation of endoplasmic reticulum stress in islets of diabetic rats. J. Pharmacol. Sci., 111, 361–371 (2009).
Lin, F. and Wang, R., Molecular modeling of the threedimensional structure of GLP-1R and its interactions with several agonists. J. Mol. Model., 15, 53–65 (2009).
Lovshin, J. A. and Drucker, D. J., Incretin-based therapies for type 2 diabetes mellitus. Nat. Rev. Endocrinol., 5, 262–269 (2009).
Phillippe, J. and Raccah, D., Treating type 2 diabetes: How safe are current therapeutic agents? Int. J. Clin. Pract., 63, 321–332 (2009).
Sloop, K. W., Willard, F. S., Brenner, M. B., Ficorilli, J., Valasek, K., Showalter, A. D., Farb, T. B., Julia, X. C., Cao, J. X. C., Cox, A. L., Michael, M. D., Sanfeliciano, S. M. G., Tebbe, M. J., and Coghlan, M. J., Novel small molecule glucagon-like peptide-1 receptor agonist stimulates insulin secretion in rodents and from human Islets. Diabetes, 59, 3099–3107 (2010).
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Edited by Mi-Kyoung Kwak, College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea Tel: 82-53-810-2823, E-mail: mkwak@ynu.ac.kr
Moon-Ho Son Director, Drug Discovery Research Laboratories, Dong-A Pharm. Co., LTD. Main Research Area
Antidiabetic agent: DPP4 inhibitor, non-peptide GPCR agonist Antiobesity agent
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Moon, HS., Kim, MK. & Son, MH. The development of non-peptide glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes. Arch. Pharm. Res. 34, 1041–1043 (2011). https://doi.org/10.1007/s12272-011-0721-z
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DOI: https://doi.org/10.1007/s12272-011-0721-z