Novel Antitumor and Nuroprotective Substances Discovered by Characteristic Screenings Based on Specific Molecular Targets

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  • SHIN-YA Kazuo
    Institute of Molecular and Cellular Biosciences, The University of Tokyo Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST)

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  • Novel Antitumor and Neuroprotective Substances Discovered by Characteristic Screenings Based on Specific Molecular Targets

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In the course of characteristic screening for antitumor substances, we isolated novel inhibitors against telomerase and the expression of molecular chaperone GRP78, designated telomestatin and versipelostatin, respectively. Telomestatin specifically acts on telomere sequence to stabilize the specific DNA structure called G-quadruplex and shows unique biological aspects that induce telomere dysfunction. Versipelostatin decreased the expression of GRP78 accompanied by a high level of cell death under glucose deprived conditions that mimicked the circumstances of a solid tumor.<BR>Furthermore, a screening program for glutamate receptor antagonist to treat brain stroke resulted in the isolation of an AMPA/NMDA antagonist kaitocephalin. Kaitocephalin potently protected rat hippocampal neurons from kainate, AMPA, and NMDA excitotoxicity. It also inhibited the Ca2+ influx elicited by AMPA and NMDA, but not by kainate.<BR>Detailed analysis for the mode of action mechanism of these compounds indicated novel and unique biological phenomena not revealed by molecular biological techniques.

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