Synthesis and Evaluation of Aryloxy-Acetamide Derivatives as CBX2 Inhibitors

Abstract

The CBX2 protein plays a key role in the methylation of histone lysine residues related to epigenetic silencing. In contrast to other polycomb paralogs, there are few examples of CBX2 modulators, which prompted us to develop small-molecule CBX2 inhibitors by synthetic evolution based on virtual screening hit scaffolds previously reported by our group. We synthesized a series of aryloxy-acetamide derivatives and evaluated their CBX2 inhibitory activities using the NanoBRET assay and the subsequent NanoBiT assay. Through structural modifications, compound 16 was identified as the best CBX2 inhibitor in this series.

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BibTeX RIS

BibTeX

@article{kawamoto2026synthesis,
  title = {{Synthesis and Evaluation of Aryloxy-Acetamide Derivatives as CBX2 Inhibitors}},
  author = {Yuichiro Kawamoto and Shohei Takase and Ashutosh Kumar and Yuki Maemoto and Kam Y J Zhang and Hisanaka Ito and Akihiro Ito},
  journal = {Chemical and Pharmaceutical Bulletin},
  year = {2026},
  month = oct,
  doi = {10.1248/cpb.c26-00135},
  url = {https://www.jstage.jst.go.jp/article/cpb/74/10/74_c26-00135/_article},
  note = {CC BY-NC},
}

RIS

TY  - JOUR
TI  - Synthesis and Evaluation of Aryloxy-Acetamide Derivatives as CBX2 Inhibitors
AU  - Yuichiro Kawamoto
AU  - Shohei Takase
AU  - Ashutosh Kumar
AU  - Yuki Maemoto
AU  - Kam Y J Zhang
AU  - Hisanaka Ito
AU  - Akihiro Ito
PY  - 2026
DA  - 2026/10/16
JO  - Chemical and Pharmaceutical Bulletin
DO  - 10.1248/cpb.c26-00135
UR  - https://www.jstage.jst.go.jp/article/cpb/74/10/74_c26-00135/_article
AB  - The CBX2 protein plays a key role in the methylation of histone lysine residues related to epigenetic silencing. In contrast to other polycomb paralogs, there are few examples of CBX2 modulators, which prompted us to develop small-molecule CBX2 inhibitors by synthetic evolution based on virtual screening hit scaffolds previously reported by our group. We synthesized a series of aryloxy-acetamide derivatives and evaluated their CBX2 inhibitory activities using the NanoBRET assay and the subsequent NanoBiT assay. Through structural modifications, compound 16 was identified as the best CBX2 inhibitor in this series.
SN  - 1347-5223
SN  - 0009-2363
ER  -

Abstract

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