Literature DB >> 21875806

Structure-activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators.

Xuechao Xing1, Ling-Chu Chang, Qiongman Kong, Craig K Colton, Liching Lai, Marcie A Glicksman, Chien-Liang Glenn Lin, Gregory D Cuny.   

Abstract

Excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter and functions to remove glutamate from synapses. A thiopyridazine derivative has been found to increase EAAT2 protein levels in astrocytes. A structure-activity relationship study revealed that several components of the molecule were required for activity, such as the thioether and pyridazine. Modification of the benzylthioether resulted in several derivatives (7-13, 7-15 and 7-17) that enhanced EAAT2 levels by >6-fold at concentrations < 5 μM after 24h. In addition, one of the derivatives (7-22) enhanced EAAT2 levels 3.5-3.9-fold after 24h with an EC(50) of 0.5 μM.
Copyright © 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 21875806      PMCID： PMC3172717          DOI： 10.1016/j.bmcl.2011.08.009

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  11 in total

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2.  Identification of translational activators of glial glutamate transporter EAAT2 through cell-based high-throughput screening: an approach to prevent excitotoxicity.

Authors:  Craig K Colton; Qiongman Kong; Liching Lai; Michael X Zhu; Kathleen I Seyb; Gregory D Cuny; Jun Xian; Marcie A Glicksman; Chien-Liang Glenn Lin
Journal:  J Biomol Screen       Date:  2010-05-27

3.  A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners.

Authors:  Banavara L Mylari; Sandra J Armento; David A Beebe; Edward L Conn; James B Coutcher; Michael S Dina; Melissa T O'Gorman; Michael C Linhares; William H Martin; Peter J Oates; David A Tess; Gregory J Withbroe; William J Zembrowski
Journal:  J Med Chem       Date:  2005-10-06       Impact factor: 7.446

4.  Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer's disease.

Authors:  Guilian Tian; Qiongman Kong; Liching Lai; Abhik Ray-Chaudhury; Chien-liang G Lin
Journal:  J Neurochem       Date:  2010-02-27       Impact factor: 5.372

5.  Translational control of glial glutamate transporter EAAT2 expression.

Authors:  Guilian Tian; Liching Lai; Hong Guo; Yuan Lin; Matthew E R Butchbach; Yueming Chang; Chien-Liang Glenn Lin
Journal:  J Biol Chem       Date:  2006-11-30       Impact factor: 5.157

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Review 7.  Astrocyte dysfunction in epilepsy.

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8.  Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice.

Authors:  Hong Guo; Liching Lai; Matthew E R Butchbach; Michael P Stockinger; Xiu Shan; Georgia A Bishop; Chien-liang Glenn Lin
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9.  A general solution for unstable boronic acids: slow-release cross-coupling from air-stable MIDA boronates.

Authors:  David M Knapp; Eric P Gillis; Martin D Burke
Journal:  J Am Chem Soc       Date:  2009-05-27       Impact factor: 15.419

Review 10.  The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention.

Authors:  Amanda L Sheldon; Michael B Robinson
Journal:  Neurochem Int       Date:  2007-04-19       Impact factor: 3.921
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  19 in total

Review 1.  Glutamate transporter 1: target for the treatment of alcohol dependence.

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2.  The preclinical discovery of amyotrophic lateral sclerosis drugs.

Authors:  Marcie A Glicksman
Journal:  Expert Opin Drug Discov       Date:  2011-10-25       Impact factor: 6.098

3.  Translational enhancers of EAAT2: therapeutic implications for neurodegenerative disease.

Authors:  Allison S Limpert; Nicholas D P Cosford
Journal:  J Clin Invest       Date:  2014-02-24       Impact factor: 14.808

4.  Small-molecule activator of glutamate transporter EAAT2 translation provides neuroprotection.

Authors:  Qiongman Kong; Ling-Chu Chang; Kou Takahashi; Qibing Liu; Delanie A Schulte; Liching Lai; Brian Ibabao; Yuchen Lin; Nathan Stouffer; Chitra Das Mukhopadhyay; Xuechao Xing; Kathleen I Seyb; Gregory D Cuny; Marcie A Glicksman; Chien-Liang Glenn Lin
Journal:  J Clin Invest       Date:  2014-02-24       Impact factor: 14.808

Review 5.  Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease.

Authors:  Kou Takahashi; Joshua B Foster; Chien-Liang Glenn Lin
Journal:  Cell Mol Life Sci       Date:  2015-06-02       Impact factor: 9.261

6.  Increased glial glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus.

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Journal:  Neurobiol Dis       Date:  2012-04-06       Impact factor: 5.996

7.  Design and Characterization of Novel Small Molecule Activators of Excitatory Amino Acid Transporter 2.

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8.  Glutamate transporter EAAT2: a new target for the treatment of neurodegenerative diseases.

Authors:  Chien-Liang Glenn Lin; Qiongman Kong; Gregory D Cuny; Marcie A Glicksman
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Review 9.  Targeting the glutamatergic system for the treatment of HIV-associated neurocognitive disorders.

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10.  Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS).

Authors:  Allison S Limpert; Margrith E Mattmann; Nicholas D P Cosford
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