A small-molecule inhibitor of NF-{kappa}B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury [Research]

Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-B-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo. Furthermore, in vivo administration of B022 protected against not only NIK but also CCl₄-induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.—Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small-molecule inhibitor of NF-B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.

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