Literature DB >> 17079143

Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits.

Wenhui Hu1, Hantamalala Ralay Ranaivo, Saktimayee M Roy, Heather A Behanna, Laura K Wing, Lenka Munoz, Ling Guo, Linda J Van Eldik, D Martin Watterson.   

Abstract

We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

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Year:  2006        PMID: 17079143      PMCID: PMC1868432          DOI: 10.1016/j.bmcl.2006.10.028

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


  20 in total

1.  Characteristic physical properties and structural fragments of marketed oral drugs.

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Review 2.  Anti-TNF-alpha therapies: they are all the same (aren't they?).

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Review 3.  Drug discovery: selecting the optimal approach.

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Journal:  Drug Discov Today       Date:  2006-05       Impact factor: 7.851

Review 4.  Anti-cytokine therapy for rheumatoid arthritis.

Authors:  R N Maini; P C Taylor
Journal:  Annu Rev Med       Date:  2000       Impact factor: 13.739

Review 5.  Neuroinflammation: a potential therapeutic target.

Authors:  Jeffrey M Craft; D Martin Watterson; Linda J Van Eldik
Journal:  Expert Opin Ther Targets       Date:  2005-10       Impact factor: 6.902

Review 6.  Glia and their cytokines in progression of neurodegeneration.

Authors:  Robert E Mrak; W Sue T Griffin
Journal:  Neurobiol Aging       Date:  2005-03       Impact factor: 4.673

7.  Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration.

Authors:  Hantamalala Ralay Ranaivo; Jeffrey M Craft; Wenhui Hu; Ling Guo; Laura K Wing; Linda J Van Eldik; D Martin Watterson
Journal:  J Neurosci       Date:  2006-01-11       Impact factor: 6.167

8.  3-aminopyridazine derivatives with atypical antidepressant, serotonergic, and dopaminergic activities.

Authors:  C G Wermuth; G Schlewer; J J Bourguignon; G Maghioros; M J Bouchet; C Moire; J P Kan; P Worms; K Biziere
Journal:  J Med Chem       Date:  1989-03       Impact factor: 7.446

Review 9.  De novo and molecular target-independent discovery of orally bioavailable lead compounds for neurological disorders.

Authors:  Laura K Wing; Heather A Behanna; Linda J Van Eldik; D Martin Watterson; Hantamalala Ralay Ranaivo
Journal:  Curr Alzheimer Res       Date:  2006-07       Impact factor: 3.498

Review 10.  Epilepsy after head injury.

Authors:  Raimondo D'Ambrosio; Emilio Perucca
Journal:  Curr Opin Neurol       Date:  2004-12       Impact factor: 5.710

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  30 in total

1.  A swell in the armamentarium of antiepileptic drug targets.

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Journal:  Epilepsy Curr       Date:  2011-11       Impact factor: 7.500

2.  Inhibition of experimental autoimmune encephalomyelitis by a novel small molecular weight proinflammatory cytokine suppressing drug.

Authors:  William J Karpus; Nathaneal Reynolds; Heather A Behanna; Linda J Van Eldik; D Martin Watterson
Journal:  J Neuroimmunol       Date:  2008-10-15       Impact factor: 3.478

3.  Closed head injury in an age-related Alzheimer mouse model leads to an altered neuroinflammatory response and persistent cognitive impairment.

Authors:  Scott J Webster; Linda J Van Eldik; D Martin Watterson; Adam D Bachstetter
Journal:  J Neurosci       Date:  2015-04-22       Impact factor: 6.167

4.  Molecular properties and CYP2D6 substrates: central nervous system therapeutics case study and pattern analysis of a substrate database.

Authors:  Laura K Chico; Heather A Behanna; Wenhui Hu; Guifa Zhong; Saktimayee Mitra Roy; D Martin Watterson
Journal:  Drug Metab Dispos       Date:  2009-08-06       Impact factor: 3.922

5.  Minozac treatment prevents increased seizure susceptibility in a mouse "two-hit" model of closed skull traumatic brain injury and electroconvulsive shock-induced seizures.

Authors:  MaryAnn Chrzaszcz; Charu Venkatesan; Tina Dragisic; D Martin Watterson; Mark S Wainwright
Journal:  J Neurotrauma       Date:  2010-07       Impact factor: 5.269

6.  An anti-neuroinflammatory that targets dysregulated glia enhances the efficacy of CNS-directed gene therapy in murine infantile neuronal ceroid lipofuscinosis.

Authors:  Shannon L Macauley; Andrew M S Wong; Charles Shyng; David P Augner; Joshua T Dearborn; Yewande Pearse; Marie S Roberts; Stephen C Fowler; Jonathan D Cooper; D Martin Watterson; Mark S Sands
Journal:  J Neurosci       Date:  2014-09-24       Impact factor: 6.167

7.  Identification of aminopyridazine-derived antineuroinflammatory agents effective in an Alzheimer's mouse model.

Authors:  Wei Zhou; Guifa Zhong; Xiurong Rao; Hui Xie; Shaogao Zeng; Tianyan Chi; Libo Zou; Donghai Wu; Wenhui Hu
Journal:  ACS Med Chem Lett       Date:  2012-09-04       Impact factor: 4.345

Review 8.  Human herpes virus 6B: a possible role in epilepsy?

Authors:  William H Theodore; Leon Epstein; William D Gaillard; Shlomo Shinnar; Mark S Wainwright; Steven Jacobson
Journal:  Epilepsia       Date:  2008-07-08       Impact factor: 5.864

9.  Further studies on 2-arylacetamide pyridazin-3(2H)-ones: design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists.

Authors:  Maria Paola Giovannoni; Igor A Schepetkin; Agostino Cilibrizzi; Letizia Crocetti; Andrei I Khlebnikov; Claes Dahlgren; Alessia Graziano; Vittorio Dal Piaz; Liliya N Kirpotina; Serena Zerbinati; Claudia Vergelli; Mark T Quinn
Journal:  Eur J Med Chem       Date:  2013-04-08       Impact factor: 6.514

Review 10.  The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target.

Authors:  Aaron S Borders; Lucia de Almeida; Linda J Van Eldik; D Martin Watterson
Journal:  BMC Neurosci       Date:  2008-12-03       Impact factor: 3.288

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