論文

査読有り 国際誌
2021年2月16日

Design, Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

ChemMedChem
  • Tetsuya Iida
  • ,
  • Yukihiro Itoh
  • ,
  • Yukari Takahashi
  • ,
  • Yasunobu Yamashita
  • ,
  • Takashi Kurohara
  • ,
  • Yuka Miyake
  • ,
  • Makoto Oba
  • ,
  • Takayoshi Suzuki

16
10
開始ページ
1609
終了ページ
1618
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/cmdc.202000933
出版者・発行元
Wiley

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b, which was designed based on compound 1, degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1. These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.

リンク情報
DOI
https://doi.org/10.1002/cmdc.202000933
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33470543
URL
https://onlinelibrary.wiley.com/doi/pdf/10.1002/cmdc.202000933
URL
https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cmdc.202000933
ID情報
  • DOI : 10.1002/cmdc.202000933
  • ISSN : 1860-7179
  • eISSN : 1860-7187
  • PubMed ID : 33470543

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