G Protein-Coupled Receptor 119 (GPR119) Agonists for the Treatment of Diabetes: Recent Progress and Prevailing Challenges
| Autor: | Kurt Ritter, Christoph Pöverlein, Lothar Schwink, Christian Buning, Nis Halland |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Clinical Trials as Topic Chemistry business.industry Pharmacology Ligands Body weight medicine.disease Receptors G-Protein-Coupled 03 medical and health sciences Safety profile 030104 developmental biology GPR119 Diabetes mellitus Drug Discovery Diabetes Mellitus medicine Humans Molecular Medicine business G protein-coupled receptor Pharmaceutical industry |
| Zdroj: | Journal of Medicinal Chemistry. 59:3579-3592 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.5b01198 |
| Popis: | In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in the search for GPR119 agonists, making it a highly competitive area in the industrial environment. Several GPR119 agonists have been entered into clinical studies, but many have failed either in phase I or II and none has progressed beyond phase II. Herein we describe the strategies chosen by the different medicinal chemistry teams in academia and the pharmaceutical industry to improve potency, physicochemical properties, pharmacokinetics, and the safety profile of GPR119 agonists in the discovery phase in order to improve the odds for successful development. |
| Databáze: | OpenAIRE |
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