title: A combined bioinformatics and chemoinformatics approach for developing asymmetric bivalent AMPA receptor positive allosteric modulators as neuroprotective agents.
abstract: 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.
authors.affiliation: Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Chen
authors.forename: Cheng Z
authors.initials: CZ
authors.lastname: Wang
authors.forename: Chunyong
authors.initials: C
authors.lastname: Ding
authors.forename: Christopher
authors.initials: C
authors.lastname: Wild
authors.forename: Bryan
authors.initials: B
authors.lastname: Copits
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Swanson
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Johnson
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid