Zopolrestat as a Human Glyoxalase I Inhibitor and Its Structural Basis

Authors

  • Jing Zhai,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Hong Zhang,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Ligping Zhang,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Yining Zhao,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Dr. Sangke Chen,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Yunyun Chen,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Xinyu Peng,

    1. Institute of Animal Health, Guangdong Academy of Agricultural Sciences, 28 Jinying Rd, Tianhe, Guangzhou, Guangdong 510640 (P.R. China)
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  • Prof. Qing Li,

    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
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  • Dr. Minggui Yuan,

    Corresponding author
    1. Institute of Animal Health, Guangdong Academy of Agricultural Sciences, 28 Jinying Rd, Tianhe, Guangzhou, Guangdong 510640 (P.R. China)
    • Minggui Yuan, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, 28 Jinying Rd, Tianhe, Guangzhou, Guangdong 510640 (P.R. China)

      Xiaopeng Hu, Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)

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  • Prof. Xiaopeng Hu

    Corresponding author
    1. Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)
    • Minggui Yuan, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, 28 Jinying Rd, Tianhe, Guangzhou, Guangdong 510640 (P.R. China)

      Xiaopeng Hu, Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (P.R. China)

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Abstract

original image

Old drugs new tricks: Zopolrestat, an aldose reductase inhibitor developed by Pfizer for the treatment of diabetic complications, is a potent competition inhibitor of human glyoxalase I (GLOI) in vitro. Crystal structures of GLOI in complex with zopolrestat and indomethacin, a nonsteroidal anti-inflammatory drug and moderate inhibitor of GLOI, provide a structural basis for the development of novel GLOI inhibitors with excellent pharmacokinetics profiles.

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