Search

Your search keyword '"Joanne J. Bronson"' showing total 6 results
Start Over Author "Joanne J. Bronson" Publisher american chemical society
6 results on '"Joanne J. Bronson"'

1. Discovery and Preclinical Evaluation of BMS-955829, a Potent Positive Allosteric Modulator of mGluR5

Author

Amy Easton, Jeffrey M. Brown, Valerie J. Whiterock, Yanling Huang, Gail K. Mattson, Kelli M. Jones, Michele Matchett, Arun K. Senapati, Andrew P. Degnan, Frank J. Simutis, Yu-Wen Li, Lawrence B. Snyder, Alda Fernandes, Digavalli V. Sivarao, Anand Balakrishnan, Umesh Hanumegowda, Kenneth S. Santone, Eric Shields, Regina Miller, Joanne J. Bronson, Ryan Westphal, Michael Gulianello, John E. Macor, Hong Huang, and Fukang Yang

Subjects
0301 basic medicine, Agonist, Allosteric modulator, medicine.drug_class, Metabotropic glutamate receptor 5, Organic Chemistry, Allosteric regulation, Neurotoxicity, Glutamate receptor, Biology, Pharmacology, medicine.disease, Biochemistry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Metabotropic glutamate receptor, mental disorders, Drug Discovery, medicine, Potency, 030217 neurology & neurosurgery
Abstract

Positive allosteric modulators (PAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5) are of interest due to their potential therapeutic utility in schizophrenia and other cognitive disorders. Herein we describe the discovery and optimization of a novel oxazolidinone-based chemotype to identify BMS-955829 (4), a compound with high functional PAM potency, excellent mGluR5 binding affinity, low glutamate fold shift, and high selectivity for the mGluR5 subtype. The low fold shift and absence of agonist activity proved critical in the identification of a molecule with an acceptable preclinical safety profile. Despite its low fold shift, 4 retained efficacy in set shifting and novel object recognition models in rodents.

Published
2016

2. Nucleotide Analogues as Antiviral Agents

Author

JOHN C. MARTIN, Charles E. McKenna, Jeffrey N. Levy, Leslie A. Khawli, Vahak Harutunian, Ting-Gao Ye, Milbrey C. Starnes, Ashok Bapat, Yung-Chi Cheng, E. J. Reist, P. A. Sturm, R. Y. Pong, M. J. Tanga, R. W. Sidwell, Richard L. Tolman, Antonin Holý, Erik De Clercq, Ivan Votruba, Joanne J. Bronson, C

Published
1989

5. Enhancing the Visibility of Women in the ACS Division of Medicinal Chemistry (ACS MEDI).

Author

Aldrich J, Allen S, Araujo E, Bronson J, Bryant-Friedrich A, Cyr SK, DiMauro EF, Dzierba C, Garner AL, Georg GI, Goodwin NC, Haranahalli K, Huang R, Leftheris K, May-Dracka TL, Olson ME, and Blanco MJ

Subjects
Humans, Female, United States, Chemistry, Pharmaceutical
Abstract

On the occasion of the 2023 International Women's Day on March 8, 2023, we want to celebrate and highlight the contributions of many women volunteers in the American Chemical Society Division of Medicinal Chemistry (ACS MEDI).

Published
2023
Full Text
View/download PDF

6. Small molecule receptor protein tyrosine phosphatase γ (RPTPγ) ligands that inhibit phosphatase activity via perturbation of the tryptophan-proline-aspartate (WPD) loop.

Author

Sheriff S, Beno BR, Zhai W, Kostich WA, McDonnell PA, Kish K, Goldfarb V, Gao M, Kiefer SE, Yanchunas J, Huang Y, Shi S, Zhu S, Dzierba C, Bronson J, Macor JE, Appiah KK, Westphal RS, O'Connell J, and Gerritz SW

Subjects
Amino Acid Sequence, Catalytic Domain, Crystallography, X-Ray, Humans, Hydrophobic and Hydrophilic Interactions, Ligands, Molecular Sequence Data, Protein Binding, Protein Conformation, Receptor-Like Protein Tyrosine Phosphatases, Class 5 chemistry, Structure-Activity Relationship, Thiophenes chemical synthesis, Models, Molecular, Receptor-Like Protein Tyrosine Phosphatases, Class 5 antagonists & inhibitors, Thiophenes chemistry
Abstract

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase γ (RPTPγ) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTPγ, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.

Published
2011
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results