Discovery, optimisation and in vivo evaluation of novel GPR119 agonists
| Autor: | David S. Clarke, Andrew G. Leach, Hayley S. Brown, Roger John Butlin, Simon M. Poucher, Charles John O'donnell, Anders Broo, James S. Scott, Sam D. Groombridge, Katy J. Brocklehurst, Darren Mckerrecher, Elizabeth E. Kelly, Leanne Westgate, Matt J.M. Wood, Kristin Goldberg, Öjvind Davidsson, Joanne Teague, Paul Schofield |
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| Rok vydání: | 2011 |
| Předmět: |
ERG1 Potassium Channel
Transgene Clinical Biochemistry hERG Drug Evaluation Preclinical Pharmaceutical Science Administration Oral Pharmacology Biochemistry Diabetes Mellitus Experimental Receptors G-Protein-Coupled Type ii diabetes Mice Structure-Activity Relationship Pharmacokinetics In vivo Drug Discovery Animals Humans Hypoglycemic Agents Receptor Molecular Biology Mice Knockout biology Drug discovery Organic Chemistry Ether-A-Go-Go Potassium Channels Mice Inbred C57BL GPR119 biology.protein Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(24) |
| ISSN: | 1464-3405 |
| Popis: | GPR119 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. During a programme aimed at developing agonists of the GPR119 receptor, we identified compounds that were potent with reduced hERG liabilities, that had good pharmacokinetic properties and that displayed excellent glucose-lowering effects in vivo. However, further profiling in a GPR119 knock-out (KO) mouse model revealed that the biological effects were not exclusively due to GPR119 agonism, highlighting the value of transgenic animals in drug discovery programs. |
| Databáze: | OpenAIRE |
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