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Your search keyword '"Elise Gadouleau"' showing total 4 results
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4 results on '"Elise Gadouleau"'

1. Design and Evaluation of [18F]CHDI-650 as a Positron Emission Tomography Ligand to Image Mutant Huntingtin Aggregates

Author

Longbin Liu, Peter D. Johnson, Michael E. Prime, Vinod Khetarpal, Christopher J. Brown, Luca Anzillotti, Daniele Bertoglio, Xuemei Chen, Samuel Coe, Randall Davis, Anthony P. Dickie, Simone Esposito, Elise Gadouleau, Paul R. Giles, Catherine Greenaway, James Haber, Christer Halldin, Scott Haller, Sarah Hayes, Todd Herbst, Frank Herrmann, Manuela Heßmann, Ming Min Hsai, Yaser Khani, Adrian Kotey, Angelo Lembo, John E. Mangette, Gwendolyn A. Marriner, Richard W. Marston, Matthew R. Mills, Edith Monteagudo, Anton Forsberg-Morén, Sangram Nag, Laura Orsatti, Christine Sandiego, Sabine Schaertl, Joanne Sproston, Steven Staelens, Jack Tookey, Penelope A. Turner, Andrea Vecchi, Maria Veneziano, Ignacio Muñoz-Sanjuan, Jonathan Bard, and Celia Dominguez

Subjects
Drug Discovery, Molecular Medicine, Settore CHIM/08 - Chimica Farmaceutica, Settore CHIM/06
Published
2022

2. Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa

Author

Denes Haase, John W. Cuozzo, John Barker, Pia Thommes, Michael Zahn, Avery Hunt, Vasileios Roumpelakis, Ying Zhang, Emily Trimby, Elise Gadouleau, Alain Dorali, Kostas Papadopoulos, Ole A. Andersen, Christoph E. Dumelin, Christel Compper, Michelle Southey, Christopher Lumley, Eric A. Sigel, Paolo A. Centrella, Barbara Mertins, Maisie Holbrow-Wilshaw, Spencer Napier, Adele Faulkner, Magali Dejob, Timothy Gorman, Alastair L Parkes, Boudewijn Dejonge, Thomas Krulle, Ricky Cain, Jennifer Williams, Boer Deng, Olivier Barbeau, Anthony D. Keefe, Sian Evans, David F. Corbett, Donnya Etheridge, Daniel B. Stein, Ryan M Dominic, Dawn M. Troast, Xianfu Li, Rajesh Odedra, Matthew A. Clark, Anthony P Dickie, Holly T Soutter, Kate Spear, and Angelo Sanzone

Subjects
Biochemistry, Pseudomonas aeruginosa, Chemistry, Acyltransferase, Drug Discovery, medicine, Molecular Medicine, Potency, Antimicrobial, medicine.disease_cause, IC50, UDP-N-acetylglucosamine acyltransferase, Escherichia coli
Abstract

This study describes a novel series of UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of Pseudomonas aeruginosa LpxA with no activity against Escherichia coli LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against P. aeruginosa LpxA (best half-maximal inhibitory concentration (IC50) 20 μM and MIC > 128 μg/mL). The mode of action of analogues was confirmed through genetic analyses. As expected, compounds were active against multidrug-resistant isolates. Further optimization of pharmacokinetics is needed before efficacy studies in mouse infection models can be attempted. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa.

Published
2021

3. Discovery of Novel UDP

Author

M Dominic, Ryan, Alastair L, Parkes, David, Corbett, Anthony P, Dickie, Michelle, Southey, Ole A, Andersen, Daniel B, Stein, Olivier R, Barbeau, Angelo, Sanzone, Pia, Thommes, John, Barker, Ricky, Cain, Christel, Compper, Magali, Dejob, Alain, Dorali, Donnya, Etheridge, Sian, Evans, Adele, Faulkner, Elise, Gadouleau, Timothy, Gorman, Denes, Haase, Maisie, Holbrow-Wilshaw, Thomas, Krulle, Xianfu, Li, Christopher, Lumley, Barbara, Mertins, Spencer, Napier, Rajesh, Odedra, Kostas, Papadopoulos, Vasileios, Roumpelakis, Kate, Spear, Emily, Trimby, Jennifer, Williams, Michael, Zahn, Anthony D, Keefe, Ying, Zhang, Holly T, Soutter, Paolo A, Centrella, Matthew A, Clark, John W, Cuozzo, Christoph E, Dumelin, Boer, Deng, Avery, Hunt, Eric A, Sigel, Dawn M, Troast, and Boudewijn L M, DeJonge

Subjects
Structure-Activity Relationship, Molecular Structure, Drug Discovery, Drug Resistance, Bacterial, Pseudomonas aeruginosa, Escherichia coli, Microbial Sensitivity Tests, Enzyme Inhibitors, Crystallography, X-Ray, Acyltransferases, Anti-Bacterial Agents
Abstract

This study describes a novel series of UDP

Published
2021

4. Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand

Author

Michael Prime, Samantha Green, Celia Dominguez, Edith Monteagudo, Malcolm Taylor, Akihiro Takano, Longbin Liu, Adrian Kotey, Wayne Thomas, Zhisheng Jia, Anthony P Dickie, Catherine Greenaway, Samuel Coe, Miklós Tóth, John Wityak, Vinod Khetarpal, Sergio Menta, Simone Esposito, Katarina Vanräs, Andreas Ebneth, John E. Mangette, Ian Wigginton, Todd Herbst, Peter Johnson, Sabine Schaertl, Vladimir Stepanov, Jonathan Bard, Sebastien Galan, Elise Gadouleau, Randall Davis, Christopher John Brown, Frank Herrmann, Richard W Marston, Darshan Gunvant Vaidya, Laura Orsatti, Xuemei Chen, Martina Nibbio, Manuela Heßmann, Joanne Sproston, Matthew R Mills, Ignacio Munoz-Sanjuan, Daniel Clark-Frew, Derek Alexander Weddell, Ladislav Mrzljak, Christoph Scheich, Xinjie Gai, Christer Halldin, Sangram Nag, Lee Matthew, Patricia Miranda-Azpiazu, Paul Giles, Thomas Krulle, Alexander Kiselyov, Marie Svedberg, and Sarah Hayes

Subjects
Male, Huntingtin, Imaging biomarker, Mutant, Protein aggregation, medicine.disease_cause, Ligands, 01 natural sciences, Protein Aggregation, Pathological, Madin Darby Canine Kidney Cells, Rats, Sprague-Dawley, 03 medical and health sciences, Mice, Dogs, Drug Discovery, medicine, Animals, Humans, 030304 developmental biology, 0303 health sciences, Mutation, Huntingtin Protein, medicine.diagnostic_test, Chemistry, Ligand (biochemistry), 0104 chemical sciences, Cell biology, Mice, Inbred C57BL, 010404 medicinal & biomolecular chemistry, Disease Models, Animal, Huntington Disease, Positron emission tomography, Positron-Emission Tomography, Molecular Medicine, Female, Efflux, Radiopharmaceuticals, Peptides
Abstract

Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington's disease (HD) pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD therapeutic development and disease progression. To identify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural activity studies; lead optimization of aggregate-binding affinity, unbound fractions in brain, permeability, and low efflux culminated in the discovery of compound 1, which exhibited target engagement in autoradiography (ARG) studies in brain slices from HD mouse models and postmortem human HD samples. PET imaging studies with 11C-labeled 1 in both HD mice and WT nonhuman primates (NHPs) demonstrated that the right-hand-side labeled ligand [11C]-1R (CHDI-180R) is a suitable PET tracer for imaging of mHTT aggregates. [11C]-1R is now being advanced to human trials as a first-in-class HD PET radiotracer.

Published
2020

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