Characterization of a small-molecule inhibitor targeting NEMO/IKKβ to suppress colorectal cancer growth
oleh: 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: | Article |
|---|---|
| Diterbitkan: | Nature Publishing Group 2022-03-01 |
Deskripsi
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.