Characterization of a Small-molecule Inhibitor Targeting NEMO/IKKβ to Suppress Colorectal Cancer Growth

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2022 Mar 9

PMID 35260565

Authors

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

Affiliations

Soon will be listed here.

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 IC 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.

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