13 results on '"Anne, Chateauneuf"'
Search Results
2. 2,3-Diarylthiophenes as selective EP1 receptor antagonists
- Author
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Richard Friesen, Gillian Greig, Nicole Sawyer, Bernard Cote, Stacia Kargman, Sonia Lamontagne, Kathleen M. Metters, Richard Frenette, Yves Ducharme, Gary P. O'Neill, François Nantel, Marie-Claude Carrière, Evelyn Martins, Anne Chateauneuf, Danielle Denis, and Marc Blouin
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Clinical Biochemistry ,Pharmaceutical Science ,Thiophenes ,Pharmacology ,Biochemistry ,Chemical synthesis ,Cell Line ,Structure-Activity Relationship ,Pharmacokinetics ,In vivo ,Drug Discovery ,Animals ,Humans ,Receptors, Prostaglandin E ,Structure–activity relationship ,Tissue Distribution ,Receptor ,Molecular Biology ,Chemistry ,Organic Chemistry ,Antagonist ,Brain ,Receptors, Prostaglandin E, EP1 Subtype ,In vitro ,Rats ,Cell culture ,Molecular Medicine ,Half-Life - Abstract
The synthesis and the EP(1) receptor binding affinity of 2,3-diarylthiophene derivatives are described. The evaluation of the structure-activity relationship (SAR) in this series led to the identification of compounds 4, 7, and 12a, which exhibit high affinity for the human EP(1) receptor and a selectivity greater than 100-fold against the EP(2), EP(3), EP(4), DP, FP, and IP receptors and greater than 25-fold versus the TP receptor. These three antagonists present good pharmacokinetics in rats and significant differences in the way they are distributed in the brain.
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- 2005
3. Molecular pharmacology of the human prostaglandin D2receptor, CRTH2
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Elizabeth Cauchon, Nicole Sawyer, François G. Gervais, Rani P.G. Cruz, Gary P. O'Neill, Donald W. Nicholson, Kathleen M. Metters, and Anne Chateauneuf
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Pharmacology ,education.field_of_study ,Ligand binding assay ,Population ,respiratory system ,Biology ,Molecular biology ,Dissociation constant ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Potency ,lipids (amino acids, peptides, and proteins) ,Prostaglandin D2 ,Binding site ,Receptor ,education ,Prostaglandin D2 receptor - Abstract
1. The recombinant human prostaglandin D(2) (PGD(2)) receptor, hCRTH2, has been expressed in HEK293(EBNA) and characterized with respect to radioligand binding and signal transduction properties. High and low affinity binding sites for PGD(2) were identified in the CRTH2 receptor population by saturation analysis with respective equilibrium dissociation constants (K(D)) of 2.5 and 109 nM. This revealed that the affinity of PGD(2) for CRTH2 is eight times less than its affinity for the DP receptor. 2. Equilibrium competition binding assays revealed that of the compounds tested, only PGD(2) and several related metabolites bound with high affinity to CRTH2 (K(i) values ranging from 2.4 to 34.0 nM) with the following rank order of potency: PGD(2)>13,14-dihydro-15-keto PGD(2)>15-deoxy-Delta(12,14)-PGJ(2)>PGJ(2)>Delta(12)-PGJ(2)>15(S)-15 methyl-PGD(2). This is in sharp contrast with the rank order of potency obtained at DP : PGD(2)>PGJ(2)>Delta(12)-PGJ(2)>15-deoxy-Delta(12,14)-PGJ(2) >>>13,14-dihydro-15-keto-PGD(2). 3. Functional studies demonstrated that PGD(2) activation of recombinant CRTH2 results in decrease of intracellular cAMP in a pertussis toxin-sensitive manner. Therefore, we showed that CRTH2 can functionally couple to the G-protein G(alphai/o). PGD(2) and related metabolites were tested and their rank order of potency followed the results of the membrane binding assay. 4. By Northern blot analysis, we showed that, besides haemopoietic cells, CRTH2 is expressed in many other tissues such as brain, heart, thymus, spleen and various tissues of the digestive system. In addition, in situ hybridization studies revealed that CRTH2 mRNA is expressed in human eosinophils. Finally, radioligand binding studies demonstrated that two eosinophilic cell lines, butyric acid-differentiated HL-60 and AML 14.3D10, also endogenously express CRTH2.
- Published
- 2002
4. Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP
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Anne Chateauneuf, Gary P. O'Neill, Rani P.G. Cruz, Stephen Gale, François G. Gervais, François Nantel, Kathleen M. Metters, and Nicole Sawyer
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Receptors, Prostaglandin ,Immunology ,Chemokinesis ,Eosinophil-derived neurotoxin ,Apoptosis ,Biology ,medicine.disease_cause ,Cell Degranulation ,chemistry.chemical_compound ,Cell Movement ,medicine ,Humans ,Immunology and Allergy ,Eosinophil degranulation ,RNA, Messenger ,Receptors, Immunologic ,Cells, Cultured ,Eosinophil cationic protein ,Prostaglandin D2 ,Degranulation ,respiratory system ,Eosinophil ,Eosinophils ,medicine.anatomical_structure ,chemistry ,Allergic response ,lipids (amino acids, peptides, and proteins) - Abstract
Background: PGD 2 is the major prostanoid released by mast cells during an allergic response. Its role in the allergic response, however, remains unclear. Objective: Because the accumulation of eosinophils is a feature of allergic reactions, we investigated the role of PGD 2 in the modulation of eosinophil function. Methods: Circulating human eosinophils were isolated and challenged with PGD 2 . The effects of PGD 2 on various eosinophil functions were then analyzed. Results: PGD 2 binds with high affinity preferentially to 2 receptors, DP and chemoattractant receptor-homologous molecule expressed on T H 2 cells (CRTH2). We show that both DP and CRTH2 are detectable on circulating eosinophils. We demonstrate that PGD 2 (1-10 nmol/L) induces a rapid change in human eosinophil morphology and an increase in chemokinesis and promotes eosinophil degranulation. These effects are induced by the CRTH2-selective agonist 13-14-dihydro-15-keto-PGD 2 (DK-PGD 2 ) but not by the DP-selective agonist BW245C. These results suggest a role for CRTH2 in the modulation of eosinophil movement and in triggering the release of cytotoxic proteins. Finally, we demonstrate that BW245C, but not DK-PGD 2 , can delay the onset of apoptosis in cultured eosinophils, presumably through interaction with DP. Conclusion: These data support the hypothesis that PGD 2 controls eosinophil functions through 2 pharmacologically distinct receptors with independent functions. Blockade of PGD 2 -mediated effects on human eosinophils may reduce the damage caused by these cells during an allergic response, but inhibition of both receptors may be required. (J Allergy Clin Immunol 2001;108:982-8.)
- Published
- 2001
5. ChemInform Abstract: Potent and Selective 5-LO Inhibitor Bearing Benzothiophene Pharmacophore: Discovery of MK-5286
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Anne Chateauneuf, Claudio Sturino, Lianhai Li, Zhaoyin Wang, Marc Ouellet, and Carl Berthelette
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chemistry.chemical_compound ,chemistry ,Triazole derivatives ,Benzothiophene ,General Medicine ,Pharmacophore ,Combinatorial chemistry - Abstract
The synthesized substituted title benzothiophene (I) is able to serve as a novel scaffold of 5-lipoxygenase (5-LO) inhibitors and is selected to advance into pre-clinical development.
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- 2011
6. Hervé Glevarec, La culture de la chambre. Préadolescence et culture contemporaine dans l'espace familial
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Anne Chateauneuf-Malclès
- Abstract
Si les pratiques culturelles des adolescents et plus generalement de la jeunesse ont deja donne lieu a un nombre consequent de travaux sociologiques depuis une vingtaine d'annees , les univers culturels et les loisirs des moins de 15 ans ont longtemps ete ignores et restent encore peu etudies . Dans La culture de la chambre, Herve Glevarec investit le champ de la sociologie de l'enfance et contribue a enrichir notre connaissance des rapports des preadolescents a la culture, prolongeant ses tr...
- Published
- 2010
7. Structure-activity relationship of triaryl propionic acid analogues on the human EP3 prostanoid receptor
- Author
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Kathleen M. Metters, Deborah Slipetz, Danielle Denis, Jean François Truchon, Michel Gallant, Nicolas Lachance, Michel Belley, Anne Chateauneuf, Marie-Claude Carrière, Marc Labelle, Nicole Sawyer, and Sonia Lamontagne
- Subjects
Stereochemistry ,Protein Conformation ,Carboxylic acid ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Cyclic AMP ,Structure–activity relationship ,Moiety ,Animals ,Humans ,Receptors, Prostaglandin E ,Receptor ,Molecular Biology ,chemistry.chemical_classification ,Chemistry ,Ligand ,Organic Chemistry ,Prostanoid ,In vitro ,Rats ,Kinetics ,Receptors, Prostaglandin E, EP3 Subtype ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Indicators and Reagents - Abstract
Potent and selective ligands for the human EP3 prostanoid receptor are described. Triaryl compounds bearing an ortho-substituted propionic acid moiety were identified as potent EP3 antagonists based on the SAR described herein. The binding affinities of key compound on all eight human prostanoid receptors is reported.
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- 2003
8. Discovery of a Potent and Selective Agonist of the Prostaglandin EP4 Receptor
- Author
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Robert N. Young, Anne Chateauneuf, Kathleen M. Metters, Gillian Greig, Deborah Slipetz, Danielle Denis, Marie Claude Mathieu, Nathalie Chauret, and Xavier Billot
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Agonist ,Stereochemistry ,medicine.drug_class ,medicine.medical_treatment ,Clinical Biochemistry ,EP4 Receptor ,Pharmaceutical Science ,Tetrazoles ,Prostaglandin ,Ring (chemistry) ,Biochemistry ,Partial agonist ,Dinoprostone ,Cell Line ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Inverse agonist ,Humans ,Receptors, Prostaglandin E ,Potency ,Prostaglandin E2 ,Receptor ,Molecular Biology ,Organic Chemistry ,Cell Membrane ,General Medicine ,Pyrrolidinones ,chemistry ,Drug Design ,Lactam ,Molecular Medicine ,Indicators and Reagents ,Receptors, Prostaglandin E, EP4 Subtype ,Endogenous agonist ,medicine.drug ,Prostaglandin E ,Half-Life ,Hormone - Abstract
Analogues of PGE(2) wherein the hydroxycyclopentanone ring has been replaced by a lactam have been prepared and evaluated as ligands for the EP(4) receptor. An optimized compound (19a) shows high potency and agonist efficacy at the EP(4) receptor and is highly selective over the other seven known prostaglandin receptors.
- Published
- 2003
9. Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2
- Author
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Nicole, Sawyer, Elizabeth, Cauchon, Anne, Chateauneuf, Rani P G, Cruz, Donald W, Nicholson, Kathleen M, Metters, Gary P, O'Neill, and Francois G, Gervais
- Subjects
integumentary system ,Gene Expression Regulation ,Receptors, Prostaglandin ,Papers ,Humans ,lipids (amino acids, peptides, and proteins) ,HL-60 Cells ,RNA, Messenger ,Receptors, Immunologic ,Transfection ,Binding, Competitive ,Recombinant Proteins ,Cell Line - Abstract
1. The recombinant human prostaglandin D(2) (PGD(2)) receptor, hCRTH2, has been expressed in HEK293(EBNA) and characterized with respect to radioligand binding and signal transduction properties. High and low affinity binding sites for PGD(2) were identified in the CRTH2 receptor population by saturation analysis with respective equilibrium dissociation constants (K(D)) of 2.5 and 109 nM. This revealed that the affinity of PGD(2) for CRTH2 is eight times less than its affinity for the DP receptor. 2. Equilibrium competition binding assays revealed that of the compounds tested, only PGD(2) and several related metabolites bound with high affinity to CRTH2 (K(i) values ranging from 2.4 to 34.0 nM) with the following rank order of potency: PGD(2)13,14-dihydro-15-keto PGD(2)15-deoxy-Delta(12,14)-PGJ(2)PGJ(2)Delta(12)-PGJ(2)15(S)-15 methyl-PGD(2). This is in sharp contrast with the rank order of potency obtained at DP : PGD(2)PGJ(2)Delta(12)-PGJ(2)15-deoxy-Delta(12,14)-PGJ(2)13,14-dihydro-15-keto-PGD(2). 3. Functional studies demonstrated that PGD(2) activation of recombinant CRTH2 results in decrease of intracellular cAMP in a pertussis toxin-sensitive manner. Therefore, we showed that CRTH2 can functionally couple to the G-protein G(alphai/o). PGD(2) and related metabolites were tested and their rank order of potency followed the results of the membrane binding assay. 4. By Northern blot analysis, we showed that, besides haemopoietic cells, CRTH2 is expressed in many other tissues such as brain, heart, thymus, spleen and various tissues of the digestive system. In addition, in situ hybridization studies revealed that CRTH2 mRNA is expressed in human eosinophils. Finally, radioligand binding studies demonstrated that two eosinophilic cell lines, butyric acid-differentiated HL-60 and AML 14.3D10, also endogenously express CRTH2.
- Published
- 2002
10. Structure-activity relationship of biaryl acylsulfonamide analogues on the human EP(3) prostanoid receptor
- Author
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Marie-Claude Carrière, Helene Juteau, Deborah Slipetz, Kathleen M. Metters, Yves Gareau, Sonia Lamontagne, C. Rochette, Claude Godbout, Rejean Ruel, Nicolas Lachance, Nicole Sawyer, Nathalie Tremblay, Gillian Greig, D. Denis, Patrick Lacombe, Michel Gallant, Marc Labelle, and Anne Chateauneuf
- Subjects
Prostaglandin E receptor 3 ,Sulfonamides ,Stereochemistry ,Organic Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Prostanoid ,Biochemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,chemistry ,Drug Discovery ,Receptors, Prostaglandin E, EP3 Subtype ,Molecular Medicine ,Structure–activity relationship ,Moiety ,Humans ,Receptors, Prostaglandin E ,lipids (amino acids, peptides, and proteins) ,Receptor ,Molecular Biology - Abstract
Potent and selective ligands for the human EP3 prostanoid receptor are described. Biaryl compounds bearing a tethered ortho substituted acidic moiety were identified as potent EP3 antagonists based on the SAR described herein. The binding affinity of key compounds on all eight human prostanoid receptors is reported.
- Published
- 2002
11. La tradition industrialiste chez les économistes français au xixe siècle : le rôle du « saint-simonisme tardif »
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Anne Chateauneuf and Michel Bellet
- Published
- 2000
12. Identification of a GABAB receptor subunit, gb2, required for functional GABAB receptor activity
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Nathalie Coulombe, Gary P. O'Neill, Lee F. Kolakowski, Eva Mezey, Nathalie Ethier, Anne Chateauneuf, Gordon Y.K. Ng, Naohiro Tsukamoto, Jilly F. Evans, Paul J. Whiting, Terry McDonald, Michael P. Johnson, Terence E. Hébert, Stacia Kargman, Richard Sullivan, Janet A. Clark, Qingyun Liu, and Tom I. Bonner
- Subjects
Azides ,Potassium Channels ,Protein Conformation ,Protein subunit ,Molecular Sequence Data ,Immune receptor ,Biology ,GABAB receptor ,Biochemistry ,Mice ,Structure-Activity Relationship ,Xenopus laevis ,Organophosphorus Compounds ,Enzyme-linked receptor ,Animals ,Humans ,Amino Acid Sequence ,RNA, Messenger ,Potassium Channels, Inwardly Rectifying ,Receptor ,Molecular Biology ,In Situ Hybridization ,Orphan receptor ,Cell Biology ,Cell biology ,Rats ,Metabotropic receptor ,nervous system ,G Protein-Coupled Inwardly-Rectifying Potassium Channels ,Receptors, GABA-B ,COS Cells ,5-HT1 receptor ,Dimerization - Abstract
G protein-coupled receptors are commonly thought to bind their cognate ligands and elicit functional responses primarily as monomeric receptors. In studying the recombinant gamma-aminobutyric acid, type B (GABAB) receptor (gb1a) and a GABAB-like orphan receptor (gb2), we observed that both receptors are functionally inactive when expressed individually in multiple heterologous systems. Characterization of the tissue distribution of each of the receptors by in situ hybridization histochemistry in rat brain revealed co-localization of gb1 and gb2 transcripts in many brain regions, suggesting the hypothesis that gb1 and gb2 may interact in vivo. In three established functional systems (inwardly rectifying K+ channel currents in Xenopus oocytes, melanophore pigment aggregation, and direct cAMP measurements in HEK-293 cells), GABA mediated a functional response in cells coexpressing gb1a and gb2 but not in cells expressing either receptor individually. This GABA activity could be blocked with the GABAB receptor antagonist CGP71872. In COS-7 cells coexpressing gb1a and gb2 receptors, co-immunoprecipitation of gb1a and gb2 receptors was demonstrated, indicating that gb1a and gb2 act as subunits in the formation of a functional GABAB receptor.
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- 1999
13. Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3
- Author
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Lin-Lin Shiao, Brian F. O'Dowd, Anne Chateauneuf, Nathalie Coulombe, Tuan V. Nguyen, Michael P. Johnson, Suzanne R. Broussard, Gary P. O'Neill, Donna L. Hreniuk, Kathleen A. Sullivan, Gordon Y.K. Ng, Mark Abramovitz, Stacia Kargman, Roy G. Smith, Lee F. Kolakowski, Marek Sawzdargo, Habibeh Khoshbouei, Carina P. Tan, Andrew D. Howard, Susan R. George, Anita Tharian, Jilly F. Evans, and Scott D. Feighner
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Receptors, Neuropeptide ,Swine ,Molecular Sequence Data ,Neuropeptide ,Galanin receptor ,Hippocampal formation ,Biology ,Ligands ,Biochemistry ,Cell Line ,Cellular and Molecular Neuroscience ,Mice ,Xenopus laevis ,Ribonucleases ,Isomerism ,Animals ,Humans ,Amino Acid Sequence ,Galanin ,Cloning, Molecular ,Dentate gyrus ,Brain ,Nucleic Acid Hybridization ,Blotting, Northern ,Molecular biology ,Rats ,Islands of Calleja ,Receptors, Galanin ,Galanin receptor 2 ,Galanin receptor 1 ,Signal Transduction - Abstract
Galanin is a 29- or 30-amino acid peptide with wide-ranging effects on hormone release, feeding behavior, smooth muscle contractility, and somatosensory neuronal function. Three distinct galanin receptor (GALR) subtypes, designated GALR1, 2, and 3, have been cloned from the rat. We report here the cloning of the human GALR2 and GALR3 genes, an initial characterization of their pharmacology with respect to radioligand binding and signal transduction pathways, and a profile of their expression in brain and peripheral tissues. Human GALR2 and GALR3 show, respectively, 92 and 89% amino acid sequence identity with their rat homologues. Radioligand binding studies with 125I-galanin show that recombinant human GALR2 binds with high affinity to human galanin (K(D) = 0.3 nM). Human GALR3 binds galanin with less affinity (IC50 of 12 nM for porcine galanin and 75 nM for human galanin). Human GALR2 was shown to couple to phospholipase C and elevation of intracellular calcium levels as assessed by aequorin luminescence in HEK-293 cells and by Xenopus melanophore pigment aggregation and dispersion assays, in contrast to human GALR1 and human GALR3, which signal predominantly through inhibition of adenylate cyclase. GALR2 mRNA shows a wide distribution in the brain (mammillary nuclei, dentate gyrus, cingulate gyrus, and posterior hypothalamic, supraoptic, and arcuate nuclei), and restricted peripheral tissue distribution with highest mRNA levels detected in human small intestine. In comparison, whereas GALR3 mRNA was expressed in many areas of the rat brain, there was abundant expression in the primary olfactory cortex, olfactory tubercle, the islands of Calleja, the hippocampal CA regions of Ammon's horn, and the dentate gyrus. GALR3 mRNA was highly expressed in human testis and was detectable in adrenal gland and pancreas. The genes for human GALR2 and 3 were localized to chromosomes 17q25 and 22q12.2-13.1, respectively.
- Published
- 1998
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