2021年7月22日
Identification of Novel Histone Deacetylase 6‐Selective Inhibitors Bearing 3,3,3‐Trifluorolactic Amide (TFLAM) Motif as a Zinc Binding Group
ChemBioChem
- 巻
- 22
- 号
- 22
- 開始ページ
- 3158
- 終了ページ
- 3163
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/cbic.202100255
- 出版者・発行元
- Wiley
Pharmacological inhibition of histone deacetylase 6 (HDAC6) is an effective therapeutic strategy for cancer and immunological diseases. Most of the previously reported HDAC6 inhibitors have a hydroxamate group as a zinc binding group (ZBG), which coordinates to the catalytic zinc ion of HDAC6. The hydroxamate group is liable to metabolically generate mutagenetic hydroxylamine; therefore, non-hydroxamate HDAC6 inhibitors would be advantageous. In this study, to identify novel non-hydroxamate HDAC6-selective inhibitors, screening of a chemical library and the subsequent structural optimization were performed, which led to the identification of HDAC6-selective inhibitors with 3,3,3-trifluorolactic amide (TFLAM) as a novel ZBG. The identified inhibitor showed potent and selective HDAC6-inhibitory activity in cells and induced regulatory T (Treg) cell differentiation.
- ID情報
-
- DOI : 10.1002/cbic.202100255
- ISSN : 1439-7633
- ORCIDのPut Code : 97378228
- PubMed ID : 34224197