Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119

Journal of Medicinal Chemistry

Volumn 51, Issue 17, 2008, Pages 5172-5175

  Semple, Graeme ^a   Fioravanti, Beatriz ^a   Pereira, Guillherme ^a   Calderon, Imelda ^a   Uy, Jane ^a   Choi, Karoline ^a   Xiong, Yifeng ^a   Ren, Albert ^a   Morgan, Michael ^a   Dave, Vibha ^a   Thomsen, William ^a   Unett, David J ^a   Xing, Charles ^a   Bossie, Stuart ^a   Carroll, Chris ^a   Chu, Zhi Liang ^a   Grottick, Andrew J ^a   Hauser, Erin K ^a   Leonard, James ^a   Jones, Robert M ^a  

^a ARENA PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 FLUORO 4 METHANESULFONYLPHENYL [6 [4 (3 ISOPROPYL[1,2,4]OXADIAZOL 5 YL) PIPERIDIN 1 YL] 5 NITROPYRIMIDIN 4 YL]AMINE; AR 231453; CYCLIC AMP; G PROTEIN COUPLED RECEPTOR 119; GUANINE NUCLEOTIDE BINDING PROTEIN; INCRETIN; OXADIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; DRUG ACTIVITY; DRUG EFFICACY; DRUG POTENCY; MOUSE; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; RAT; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ADMINISTRATION, ORAL; ANIMALS; BLOOD GLUCOSE; GLUCOSE TOLERANCE TEST; HUMANS; HYPOGLYCEMIC AGENTS; MICE; MOLECULAR STRUCTURE; RATS; RECEPTORS, G-PROTEIN-COUPLED; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 51849099001     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm8006867     Document Type: Article

References (13)

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10. 3 Briefly, assay buffer contained 20 mM HEPES, pH 7.4, 10 μM GTP, 0.1 mM ATP, 500 μM IBMX, 10 mM phosphocreatine, and 10 U/50 μL creatine phosphokinase. Test compound incubations were performed for 60 min at room temperature in the presence of 15 μg of membrane protein. cAMP measurements were extrapolate from a standard curve included on each assay plate.
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13. Cultured Xenopus dermal melanophores were transiently transfected with plasmid DNA encoding the GPR119 receptor and plated into clear 384-well assay plates following standard protocols. At 48 h post-transfection, the cells were treated with melatonin (10nM, 1 h) to induce pigment aggregation. Cells were then exposed to test compounds for 1 h, and the resulting GPR119-induced pigment dispersion was measured using an absorbance microplate reader. For a full description of standard protocol see: Potenza, M.; Graminski, G.; Lerner, M. A method for evaluating the effects of ligands upon Gs protein-coupled receptors using a recombinant melanophore-based bioassay. Anal. Biochem. 1992, 206, 315-322.