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23 results on '"Fourquez, Jean-Marie"'

7. Small molecule glucokinase activators disturb lipid homeostasis and induce fatty liver in rodents: a warning for therapeutic applications in humans

Author

De Ceuninck, Frédéric, Kargar, Catherine, Ilic, Catherine, Caliez, Audrey, Rolin, Jean-Olivier, Umbdenstock, Thierry, Vinson, Cédric, Combettes, Murielle, de Fanti, Brant, Harley, Elizabeth, Sadlo, Marjorie, Lefèvre, Anne-Laure, Broux, Olivier, Wierzbicki, Michel, Fourquez, Jean-Marie, Perron-Sierra, Françoise, Kotschy, András, and Ktorza, Alain

Published
2013
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9. Productive Syntheses of Privileged Scaffolds Inspired by the Recognition of a Diels–Alder Pattern Common to Three Classes of Natural Products

Author

Badarau, Eduard, primary, Reddy, K. Harsha Vardhan, additional, Loudet, Aurore, additional, Simon, Charles, additional, Trembleau, Laurent, additional, Claerhout, Stijn, additional, Pair, Etienne, additional, Massip, Stéphane, additional, Breton, Philippe, additional, Lesur, Brigitte, additional, Goldstein, Solo, additional, Fourquez, Jean‐Marie, additional, Henlin, Jean Michel, additional, and Ghosez, Léon, additional

Published
2020
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12. P3-043: COGNITIVE PROFILE OF S 68890, AN ALLOSTERIC MODULATOR OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS

Author

Danober, Laurence, primary, Dores, Guillaume Das, additional, Louis, Caroline, additional, Llopis, Karine, additional, Dumas, Nathalie, additional, Liard, Catherine, additional, Girardon, Sylvie, additional, Catherine, Le Quement, additional, Bureau, Marie, additional, Krazem, Ali, additional, Béracochéa, Daniel, additional, Pillot, Thierry, additional, Le Diguarher, Thierry, additional, Bertrand, Marc, additional, Benoist, Alain, additional, Fourquez, Jean-Marie, additional, Chollet, Anne-Marie, additional, Gloanec, Philippe, additional, and Jeggo, Ross, additional

Published
2019
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13. Stereoselective Synthesis of Oxabicyclic Pyrrolidines of Medicinal Relevance: Merging Chemoenzymatic and Catalytic Methods.

Author

Hocine, Sofiane, Montagnon, Claire, Reddy Vakiti, Jithender, Fourquez, Jean‐Marie, and Hanessian, Stephen

Subjects
RACEMIC mixtures, GRIGNARD reagents, CATALYSIS, KETONES
Abstract

Two approaches to the synthesis of an oxabicyclic pyrrolidine‐6‐one are described using enzymatic resolution and gold‐mediated catalysis as key steps toward enantiopure compounds previously reported as racemic mixtures. Addition of Grignard reagents to the ketone afforded a variety of diversified tertiary alcohols of interest for their reported pharmacological activities. [ABSTRACT FROM AUTHOR]

Published
2021
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15. COGNITIVE PROFILE OF S 68890, AN ALLOSTERIC MODULATOR OF ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTORS

Author

Danober, Laurence, Dores, Guillaume Das, Louis, Caroline, Llopis, Karine, Dumas, Nathalie, Liard, Catherine, Girardon, Sylvie, Catherine, Le Quement, Bureau, Marie, Krazem, Ali, Béracochéa, Daniel, Pillot, Thierry, Le Diguarher, Thierry, Bertrand, Marc, Benoist, Alain, Fourquez, Jean-Marie, Chollet, Anne-Marie, Gloanec, Philippe, and Jeggo, Ross

Published
2019
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17. Molecular Dynamics Simulations and Kinetic Measurements to Estimate and Predict Protein–Ligand Residence Times

Author

Mollica, Luca, primary, Theret, Isabelle, additional, Antoine, Mathias, additional, Perron-Sierra, Françoise, additional, Charton, Yves, additional, Fourquez, Jean-Marie, additional, Wierzbicki, Michel, additional, Boutin, Jean A., additional, Ferry, Gilles, additional, Decherchi, Sergio, additional, Bottegoni, Giovanni, additional, Ducrot, Pierre, additional, and Cavalli, Andrea, additional

Published
2016
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18. Small molecule glucokinase activators disturb lipid homeostasis and induce fatty liver in rodents: a warning for therapeutic applications in humans

Author

De Ceuninck, Frédéric, Kargar, Catherine, Ilic, Catherine, Caliez, Audrey, Rolin, Jean-Olivier, Umbdenstock, Thierry, Vinson, Cédric, Combettes, Murielle, Fanti, Brant, Harley, Elizabeth, Sadlo, Marjorie, Lefèvre, Anne-Laure, Broux, Olivier, Wierzbicki, Michel, Fourquez, Jean-Marie, Perron-Sierra, Françoise, Kotschy, András, and Ktorza, Alain

Subjects
Themed Section: Endothelin, Blood Glucose, Glycated Hemoglobin, Male, Enzyme Activators, Lipid Metabolism, Rats, Rats, Zucker, Fatty Liver, Rats, Sprague-Dawley, Mice, Diabetes Mellitus, Type 2, Intestinal Absorption, Cell Line, Tumor, Glucokinase, Hepatocytes, Animals, Homeostasis, Humans, Hypoglycemic Agents, Caco-2 Cells, Rats, Wistar, Cells, Cultured
Abstract

Small-molecule glucokinase activators (GKAs) are currently being investigated as therapeutic options for the treatment of type 2 diabetes (T2D). Because liver overexpression of glucokinase is thought to be associated with altered lipid profiles, this study aimed at assessing the potential lipogenic risks linked to oral GKA administration.Nine GKA candidates were qualified for their ability to activate recombinant glucokinase and to stimulate glycogen synthesis in rat hepatocytes and insulin secretion in rat INS-1E cells. In vivo activity was monitored by plasma glucose and HbA1c measurements after oral administration in rodents. Risk-associated effects were assessed by measuring hepatic and plasma triglycerides and free fatty acids, as well as plasma aminotransferases, and alkaline phosphatase.GKAs, while efficiently decreasing glycaemia in acute conditions and HbA1c levels after chronic administration in hyperglycemic db/db mice, were potent inducers of hepatic steatosis. This adverse outcome appeared as soon as 4 days after daily oral administration at pharmacological doses and was not transient. GKA treatment similarly increased hepatic triglycerides in diabetic and normoglycaemic rats, together with a pattern of metabolic phenotypes including different combinations of increased plasma triglycerides, free fatty acids, alanine and aspartyl aminotransferases, and alkaline phosphatase. GKAs belonging to three distinct structural families induced hepatic steatosis in db/db mice, arguing in favour of a target-mediated, rather than a chemical class-mediated, effect.Given the risks associated with fatty liver disease in the general population and furthermore in patients with T2D, these findings represent a serious warning for the use of GKAs in humans.This article is commented on by Rees and Gloyn, pp. 335-338 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.02201.x.

Published
2012

19. Small molecule glucokinase activators disturb lipid homeostasis and induce fatty liver in rodents: a warning for therapeutic applications in humans

Author

De Ceuninck, Frédéric, primary, Kargar, Catherine, additional, Ilic, Catherine, additional, Caliez, Audrey, additional, Rolin, Jean-Olivier, additional, Umbdenstock, Thierry, additional, Vinson, Cédric, additional, Combettes, Murielle, additional, de Fanti, Brant, additional, Harley, Elizabeth, additional, Sadlo, Marjorie, additional, Lefèvre, Anne-Laure, additional, Broux, Olivier, additional, Wierzbicki, Michel, additional, Fourquez, Jean-Marie, additional, Perron-Sierra, Françoise, additional, Kotschy, András, additional, and Ktorza, Alain, additional

Published
2012
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22. Molecular Dynamics Simulations and Kinetic Measurements to Estimate and Predict Protein–Ligand Residence Times

Author

Perron-Sierra Françoise, Yves Charton, Giovanni Bottegoni, Michel Wierzbicki, Luca Mollica, Isabelle Theret, Pierre Ducrot, Mathias Antoine, Sergio Decherchi, Andrea Cavalli, Jean Marie Fourquez, Gilles Ferry, Jean A. Boutin, Mollica, Luca, Theret, Isabelle, Antoine, Mathia, Perron-Sierra, Françoise, Charton, Yve, Fourquez, Jean-Marie, Wierzbicki, Michel, Boutin, Jean A., Ferry, Gille, Decherchi, Sergio, Bottegoni, Giovanni, Ducrot, Pierre, and Cavalli, Andrea

Subjects
Models, Molecular, 0301 basic medicine, Time Factors, Molecular Dynamics Simulation, Crystallography, X-Ray, Ligands, Residence time (fluid dynamics), Bioinformatics, 01 natural sciences, Structure-Activity Relationship, 03 medical and health sciences, Molecular dynamics, Glucokinase, 0103 physical sciences, Drug Discovery, Humans, Molecular Structure, 010304 chemical physics, Chemistry, Drug discovery, Medicine (all), Drug Discovery3003 Pharmaceutical Science, Isoenzymes, Kinetics, 030104 developmental biology, Diabetes Mellitus, Type 2, Molecular Medicine, Biological system, Protein ligand
Abstract

Ligand-target residence time is emerging as a key drug discovery parameter because it can reliably predict drug efficacy in vivo. Experimental approaches to binding and unbinding kinetics are nowadays available, but we still lack reliable computational tools for predicting kinetics and residence time. Most attempts have been based on brute-force molecular dynamics (MD) simulations, which are CPU-demanding and not yet particularly accurate. We recently reported a new scaled-MD-based protocol, which showed potential for residence time prediction in drug discovery. Here, we further challenged our procedure's predictive ability by applying our methodology to a series of glucokinase activators that could be useful for treating type 2 diabetes mellitus. We combined scaled MD with experimental kinetics measurements and X-ray crystallography, promptly checking the protocol's reliability by directly comparing computational predictions and experimental measures. The good agreement highlights the potential of our scaled-MD-based approach as an innovative method for computationally estimating and predicting drug residence times.

Published
2016
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23. Productive Syntheses of Privileged Scaffolds Inspired by the Recognition of a Diels-Alder Pattern Common to Three Classes of Natural Products.

Author

Badarau E, Reddy KHV, Loudet A, Simon C, Trembleau L, Claerhout S, Pair E, Massip S, Breton P, Lesur B, Goldstein S, Fourquez JM, Henlin JM, and Ghosez L

Subjects
Catalysis, Cycloaddition Reaction, Hydrolysis, Lactams chemistry, Biological Products chemical synthesis, Biological Products chemistry
Abstract

Identification of a common Diels-Alder pattern in three classes of bioactive natural products led us to study the synthesis and cycloaddition of a new class of cyclic dienes readily available from β,γ-unsaturated lactams. A practical and readily scalable route to the parent p-methoxybenzyl-protected 6- and 7-membered β,γ-unsaturated lactams was developed. These were readily transformed into the corresponding O-silylated dienes, which were reacted with dimethyl and diethyl fumarate to yield stereoselectively highly functionalized bicyclic adducts. These exhibited unexpected and versatile transformations upon acid hydrolysis depending on the nature of the dienophile substituents and the acid catalyst. All reactions have been performed on multigram quantities. These transformations provide a convenient, economical, and easily scalable pathway for the rapid construction of functionally and stereochemically dense privileged scaffolds for the construction of libraries of natural products-inspired molecules of pharmacological relevance., (© 2020 Wiley-VCH GmbH.)

Published
2020
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