Discovery of novel mifepristone derivatives via suppressing KLF5 expression for the treatment of triple-negative breast cancer

Yuqi Lin, Rong Liu, Ping Zhao, Jinxiang Ye, Zheng Zheng, Jingan Huang, Yingying Zhang, Yu Gao, Haiying Chen, Suling Liu, Jia Zhou, Ceshi Chen, Haijun Chen

Research output: Contribution to journalArticle

6 Scopus citations


Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers currently with a lack of targeted therapeutic drugs. Accumulating evidence supports that KLF5 represents a novel therapeutic target for the treatment of basal TNBC. Our previous studies revealed that mifepristone is capable of suppressing TNBC cell proliferation and promoting cancer cell apoptosis by inhibiting KLF5 expression. Nevertheless, its anticancer efficacy is only modest with high dose. Moreover, its main metabolite N-desmethyl mifepristone with the removal of one methyl moiety results in a significant loss of antiproliferative activity, indicating an important pharmacophore domain around this methyl moiety. To improve the pharmacokinetic properties including metabolic stability and enhance the anticancer activities, a focused compound library by altering this sensitive metabolic region of mifepristone has been designed and synthesized for scaffold repurposing and structural optimization. Compound 17 (FZU-00,004) has been identified with an attractive anticancer profile against TNBC via suppressing KLF5 expression.

Original languageEnglish (US)
Pages (from-to)354-367
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
StatePublished - Feb 25 2018



  • KLF5 expression
  • Mifepristone derivatives
  • Sensitive metabolic region
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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