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A Combined Bioinformatics and Chemoinformatics Approach for Developing Asymmetric Bivalent AMPA Receptor Positive Allosteric Modulators as Neuroprotective Agents

Authors

  • Dr. Haijun Chen,

    1. Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
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    • These authors contribute equally to this work.

  • Dr. Cheng Z. Wang,

    1. Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
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    • These authors contribute equally to this work.

  • Dr. Chunyong Ding,

    1. Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
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  • Christopher Wild,

    1. Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
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  • Dr. Bryan Copits,

    1. Molecular Pharmacology & Biological Chemistry, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, 60611 IL (USA)
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  • Prof. Geoffrey T. Swanson,

    1. Molecular Pharmacology & Biological Chemistry, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, 60611 IL (USA)
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  • Prof. Kenneth M. Johnson,

    1. Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
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  • Prof. Jia Zhou

    Corresponding author
    1. Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
    • Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555 TX (USA)
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Abstract

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PAMs new in town! An effective, combined bioinformatics and chemoinformatics approach was applied to the design of novel asymmetric bivalent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators (PAMs) with marked potency in vitro and efficacy in vivo for preventing neuroapoptosis. The novel chemotype could provide pharmacological probes and potential therapeutic agents for glutamatergic hypofunction and its related neurological and psychiatric disorders.

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