2. Academic Validation
  3. Design, synthesis and evaluation of diphenyl ether-based kaiso inhibitors with enhanced potency

Design, synthesis and evaluation of diphenyl ether-based kaiso inhibitors with enhanced potency

  • Bioorg Med Chem Lett. 2025 Jun 1:121:130158. doi: 10.1016/j.bmcl.2025.130158.
Taofeng Lin 1,  Zhongqi Li 2,  Juanchan Yuan 1,  Tinfeng Ren 1,  Wan Pang 3,  Songhui Xu 4
Affiliations

Affiliations

  • 1 College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
  • 2 Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University. Nanchang, China.
  • 3 College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address: pangwan@sit.edu.cn.
  • 4 Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University. Nanchang, China; Key Laboratory of Urinary System Diseases of Jiangxi Province, Nanchang, China. Electronic address: songhuixu007@gmail.com.
PMID: 40049243 DOI: 10.1016/j.bmcl.2025.130158
Abstract

Kaiso, a potential target for the treatment of lung Cancer. Our research focuses on Kaiso inhibitros. Through virtual screening and molecular dynamic simulations, we discovered a promising Kaiso inhibitor called compound 5 (ZINC20577650). By modifying the structure of compound 5, a series of novel Kaiso inhibitors that contain a diphenyl ether ring were synthesized. Among them, compound 20 exhibited the strongest inhibitory activity against A549 cells (IC50 = 0.34 μM). Notably, its inhibitory activity surpassed that of the positive control MIRA-1 (IC50 = 654.065 μM). Molecular docking and dynamic studies revealed that the binding of the compound's amino and ester moieties to the active site of kaiso protein, as well as the extension of the benzene ring towards the Asn561 position in the cavity, contributed significantly to its potency. These findings provide valuable insights for the development of new Kaiso inhibitors.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-173198
    Kaiso Inhibitor