DOAJ Open Access 2022

Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth

Zhenlong Yu Jian Gao Xiaolei Zhang Yulin Peng Wenlong Wei +11 lainnya

Abstrak

Abstract NEMO/IKKβ complex is a central regulator of NF-κB signaling pathway, its dissociation has been considered to be an attractive therapeutic target. Herein, using a combined strategy of molecular pharmacological phenotyping, proteomics and bioinformatics analysis, Shikonin (SHK) is identified as a potential inhibitor of the IKKβ/NEMO complex. It destabilizes IKKβ/NEMO complex with IC50 of 174 nM, thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in vivo. In addition, we also elucidated the potential target sites of SHK in the NEMO/IKKβ complex. Our study provides some new insights for the development of potent small-molecule PPI inhibitors.

Topik & Kata Kunci

Medicine Biology (General)

Penulis (16)

Zhenlong Yu

Jian Gao

Xiaolei Zhang

Yulin Peng

Wenlong Wei

Jianrong Xu

Zhenwei Li

Chao Wang

Meirong Zhou

Xiangge Tian

Lei Feng

Xiaokui Huo

Min Liu

Mingliang Ye

De-an Guo

Xiaochi Ma

Format Sitasi

APA MLA BibTeX

Yu, Z., Gao, J., Zhang, X., Peng, Y., Wei, W., Xu, J. et al. (2022). Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth. https://doi.org/10.1038/s41392-022-00888-1

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Informasi Jurnal

Tahun Terbit: 2022
Sumber Database: DOAJ
DOI: 10.1038/s41392-022-00888-1
Akses: Open Access ✓