Discovery of a novel potent GPR40 full agonist

Autor:	Eric Arnoult, Meghan Hall, Monicah A. Otieno, Hui Huang, Tonya Martin, Jose Silva, Joe Gunnet, Jianying Liu, Yuanping Wang, Shuyuan Zhao, Sanath K. Meegalla, June Xu, Alessandro Pocai, Mark R. Player, Brian Rady, S. Paul Lee
Rok vydání:	2018
Předmět:	0301 basic medicine Agonist endocrine system medicine.drug_class Clinical Biochemistry Pharmaceutical Science Stimulation CHO Cells Pharmacology Biochemistry Glucagon-Like Peptide-1 Receptor Receptors G-Protein-Coupled Mice Structure-Activity Relationship 03 medical and health sciences Cricetulus Dogs Glucuronides Piperidines In vivo Free fatty acid receptor 1 Drug Discovery medicine Animals Humans Hypoglycemic Agents Sulfones Receptor Molecular Biology Benzofurans G protein-coupled receptor Glucose lowering Molecular Structure Phenylpropionates Chemistry Biphenyl Compounds Organic Chemistry In vitro Rats Molecular Docking Simulation Macaca fascicularis Pyrimidines 030104 developmental biology Pyrazines Microsomes Liver Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 28:720-726
ISSN:	0960-894X
Popis:	Compound 12 is a GPR40 agonist that realizes the full magnitude of efficacy possible via GPR40 receptor agonism. In vitro and in vivo studies demonstrated superior glucose lowering by 12 compared to fasiglifam (TAK-875), in a glucose dependent manner. The enhanced efficacy observed with the full agonist 12 was associated with both direct and indirect stimulation of insulin secretion.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b9e2be080c63f5e0193dac4541286e1 https://doi.org/10.1016/j.bmcl.2018.01.013 Zobrazit plný text záznamu Full Text from ScienceDirect