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      https://www.ias.ac.in/article/fulltext/jcsc/133/0011

    • Keywords

       

      Benzo[d]isoxazol; BRD4; bromodomain; molecular docking

    • Abstract

       

      The BRD4 protein is associated with various diseases, which has been an attractive target for the treatment of cancer and inflammation. This paper is a follow-up to our previous studies, in which we report the structure-based design, synthesis, and evaluation of a new class of small-molecule BRD4 bromodomain inhibitors bearing a benzo[d]isoxazol scaffold. The SARs focused on exploration of the 2¢ or 3¢ position to afford novel inhibitors that may avoid potential metabolically unstable site. The most potent inhibitor 13f exhibited high binding affinity to BRD4(1) with a DTm value of 7.8 °C as evaluated in thermal shift assay (TSA). The potent activity was also demonstrated by a peptide competition assay with an IC50 value of 0.21 mM. The docking studies revealed the binding mode of the compounds with the active site of BRD4(1). In addition, in silico predictions indicated that these compounds possessed good drug-likeness and pharmacokinetic profile

    • Graphical Abstract

       

      This paper is a follow-up to our previous studies, in which we report the structure-based design, synthesis, and evaluation of a new class of small-molecule BRD4 bromodomain inhibitors bearing a benzo[d]isoxazol scaffold.
    • Author Affiliations

       

      MAOFENG ZHANG1 2 ZHUYUN LIU1 LIZHONG WANG1 2 YAN LI1 YONGGANG MA1

      1. College of Pharmacy, Taizhou Polytechnic College, Taizhou 225300, People’s Republic of China
      2. Jiangsu Solid Preparation Engineering Technology Research and Development Center, Taizhou 225300,People’s Republic of China
    • Dates

       
  • Journal of Chemical Sciences | News

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