Highlighted Paper selected by Editor-in-Chief : Novel Non-carboxylate Benzoylsulfonamide-Based Protein Tyrosine Phosphatase 1B Inhibitors with Non-competitive Actions

DOI Web Site Web Site PubMed 被引用文献3件 参考文献49件
  • Morishita Ko
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
  • Shoji Yoshimichi
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
  • Tanaka Shunkichi
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
  • Fukui Masaki
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
  • Ito Yuma
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
  • Kitao Tatsuya
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.
  • Ozawa Shin-ichiro
    School of Pharmacy, Kitasato University
  • Hirono Shuichi
    School of Pharmacy, Kitasato University
  • Shirahase Hiroaki
    Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.

書誌事項

タイトル別名
  • Novel Non-carboxylate Benzoylsulfonamide-Based Protein Tyrosine Phosphatase 1B Inhibitors with Non-competitive Actions

この論文をさがす

説明

<p>A novel series of benzoylsulfonamide derivatives were synthesized and biologically evaluated. Among them, 4-(biphenyl-4-ylmethylsulfanylmethyl)-N-(hexane-1-sulfonyl)benzamide (compound 18K) was identified as a protein tyrosine phosphatase 1B (PTP1B) inhibitor with potent and selective inhibitory activity against PTP1B (IC50=0.25 µM). Compound 18K functioned as a non-competitive inhibitor and bound to the allosteric site of PTP1B. It also showed high oral absorption in mice (the maximum drug concentration (Cmax)=45.5 µM at 30 mg/kg), rats (Cmax=53.6 µM at 30 mg/kg), and beagles (Cmax=37.8 µM at 10 mg/kg), and significantly reduced plasma glucose levels at 30 mg/kg/d (per os (p.o.)) for one week with no side effects in db/db mice. In conclusion, the substituted benzoylsulfonamide was shown to be a novel scaffold of a non-competitive and allosteric PTP1B inhibitor, and compound 18K has potential as an efficacious and safe anti-diabetic drug as well as a useful tool for investigations of the physiological and pathophysiological effects of allosteric PTP1B inhibition.</p>

収録刊行物

被引用文献 (3)*注記

もっと見る

参考文献 (49)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ