2. Academic Validation
  3. Design, synthesis and activity evaluation of quinolinone derivatives as EZH2 inhibitors

Design, synthesis and activity evaluation of quinolinone derivatives as EZH2 inhibitors

  • Bioorg Med Chem Lett. 2024 Jun 1:105:129726. doi: 10.1016/j.bmcl.2024.129726.
Jin Cai 1,  Haoyuan You 2,  Xintong Qin 2,  Yuhong Wang 2,  Wei Li 2
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China. Electronic address: caijin@seu.edu.cn.
  • 2 School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China.
PMID: 38580135 DOI: 10.1016/j.bmcl.2024.129726
Abstract

The enhancer of zeste homologue 2 (EZH2) is the core catalytic subunit of polycomb repressive complex 2, which catalyzes lysine 27 methylation of histone H3. Herein, a series of quinolinone derivatives were designed and synthesized based on the structure of Tazemetostat as the lead compound. Compound 9l (EZH2WT IC50 = 0.94 nM) showed stronger antiproliferative activity in HeLa cells than the lead compound. Moreover, compound 9e (EZH2WT IC50 = 1.01 nM) significantly inhibited the proliferation and induced Apoptosis in A549 cells.

Keywords

Anti-tumor; EZH2 inhibitor; PRC2; Quinolinone derivatives.

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