2021年2月16日
Design, Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders
ChemMedChem
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- 巻
- 16
- 号
- 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
- ID情報
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- DOI : 10.1002/cmdc.202000933
- ISSN : 1860-7179
- eISSN : 1860-7187
- PubMed ID : 33470543