@article{829ada94bc7b44e8b3087cf30edb650c,
title = "Identification of Novel Histone Deacetylase 6-Selective Inhibitors Bearing 3,3,3-Trifluorolactic Amide (TFLAM) Motif as a Zinc Binding Group",
abstract = "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.",
keywords = "HDAC6, drug discovery, fluorine, medicinal chemistry",
author = "Takashi Kurohara and Keita Tanaka and Daisuke Takahashi and Satoshi Ueda and Yasunobu Yamashita and Yuri Takada and Hirokazu Takeshima and Shengwang Yu and Yukihiro Itoh and Koji Hase and Takayoshi Suzuki",
note = "Funding Information: The authors would like to thank the members of the Comprehensive Analysis Center, SANKEN, Osaka University, for the NMR and HRMS analyses. This work was supported by the Practical Research Project for Rare/Intractable Diseases funded by the Japan Agency for Medical Research and Development (AMED; K.H., T.S.), “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT; T.S.). Funding Information: The authors would like to thank the members of the Comprehensive Analysis Center, SANKEN, Osaka University, for the NMR and HRMS analyses. This work was supported by the Practical Research Project for Rare/Intractable Diseases funded by the Japan Agency for Medical Research and Development (AMED; K.H., T.S.), “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT; T.S.). Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH.",
year = "2021",
month = nov,
day = "16",
doi = "10.1002/cbic.202100255",
language = "English",
volume = "22",
pages = "3158--3163",
journal = "ChemBioChem",
issn = "1439-4227",
publisher = "Wiley-VCH Verlag",
number = "22",
}
