3 results on '"Severine Denoyelle"'
Search Results
2. Development of non-peptidic inverse agonists of the ghrelin receptor (GHSR) based on the 1,2,4-triazole scaffold
- Author
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Sonia Cantel, Jean-Alain Fehrentz, Severine Denoyelle, Catherine Oiry, Gimena Fernandez, Mario Perello, Sylvie Peraldi-Roux, Jean-Louis Banères, Céline M'Kadmi, Guadalupe García Romero, Jacky Marie, Sophie Mary, Mathieu Maingot, Marjorie Damian, Anne-Laure Blayo, Jérémie Neasta, Khoubaib Ben Haj Salah, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Instituto Multidisciplinario de Biología Celular [La Plata] (IMBICE), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Comisión de Investigaciones Científicas [Buenos Aires] (CIC)-Universidad Nacional de la Plata [Argentine] (UNLP), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
medicine.medical_specialty ,Scaffold ,Drug Inverse Agonism ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,Carbohydrate metabolism ,Ligands ,Growth hormone ,01 natural sciences ,Islets of Langerhans ,03 medical and health sciences ,chemistry.chemical_compound ,GTP-Binding Proteins ,Internal medicine ,Insulin Secretion ,Drug Discovery ,medicine ,Animals ,Humans ,Inverse agonist ,[CHIM]Chemical Sciences ,Receptors, Ghrelin ,Receptor ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,010405 organic chemistry ,digestive, oral, and skin physiology ,1,2,4-Triazole ,Triazoles ,Ligand (biochemistry) ,Rats ,0104 chemical sciences ,HEK293 Cells ,Endocrinology ,chemistry ,Molecular Medicine ,Ghrelin - Abstract
International audience; GHSR controls, among others, growth hormone and insulin secretion, adiposity, feeding and glucose metabolism. Therefore, an inverse agonist ligand capable of selectively targeting GHSR and reducing its high constitutive activity appears to be a good candidate for the treatment of obesity-related metabolic diseases. In this context, we present a study that led to the development of several highly potent and selective inverse agonists of GHSR based on the 1,2,4-triazole scaffold. We demonstrate that, depending on the nature of the substituents on positions 3, 4 and 5, 2 this scaffold leads to ligands that exert an intrinsic inverse agonist activity on GHSR-catalyzed G protein activation through the stabilization of a specific inactive receptor conformation. Thanks to an in vivo evaluation, we also show that one of the most promising ligands not only exerts an effect on insulin secretion in rat pancreatic islets but also affects the orexigenic effects of ghrelin in mice.
- Published
- 2020
3. The 1,2,4-triazole as a scaffold for the design of ghrelin receptor ligands: development of JMV 2959, a potent antagonist
- Author
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Jean Martinez, Luc Demange, Luc Brunel, Severine Denoyelle, Johanne Ryan, Damien Boeglin, Céline M'Kadmi, Jean-Alain Fehrentz, Aline Moulin, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Laboratoire des Amino-acides Peptides et Protéines (LAPP), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Institut de Chimie de Nice (ICN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Subjects
medicine.medical_specialty ,Peptidomimetic ,Clinical Biochemistry ,Glycine ,Pharmacology ,Ligands ,Biochemistry ,Partial agonist ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Inverse agonist ,Animals ,Humans ,Receptor ,Receptors, Ghrelin ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Molecular Structure ,Chemistry ,Organic Chemistry ,Antagonist ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Triazoles ,3. Good health ,Endocrinology ,Drug Design ,Ghrelin ,Secretagogue ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery - Abstract
Ghrelin is a 28-residue peptide acylated with an n-octanoyl group on the Ser 3 residue, predominantly produced by the stomach. Ghrelin displays strong growth hormone (GH) releasing activity, which is mediated by the activation of the so-called GH secretagogue receptor type 1a (GHS-R1a). Given the wide spectrum of biological activities of Ghrelin in neuroendocrine and metabolic pathways, many research groups, including our group, developed synthetic peptide, and nonpeptide GHS-R1a ligands, acting as agonists, partial agonists, antagonists, or inverse agonists. In this highlight article, we will focus on the discovery of a GHS-R1a antagonist compound, JMV 2959, which has been extensively studied in different in vitro and in vivo models. We will first describe the peptidomimetic approach that led us to discover this compound. Then we will review the results obtained with this compound in different studies in the fields of food intake and obesity, addictive behaviors, hyperactivity and retinopathy.
- Published
- 2012
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