Development of RelB-targeting small-molecule inhibitors of non-canonical NF-κB signaling with antitumor efficacy.

ABSTRACT: Dysfunction of the non-canonical nuclear factor κB (NF-κB) signaling pathway has been causally associated with numbers of cancers and autoimmune diseases. However, specific inhibitors for this signaling pathway remain to be developed. Here, we showed that structure-based cell-based screening yielded a potent and specific small molecule targeting RelB to inhibit the non-canonical NF-κB signaling pathway, while it had no inhibitory effect on the canonical NF-κB signaling pathway. Mechanistically, the inhibitor directly interacted with RelB protein and disrupted RelB binding to its target DNA, thus repressing RelB transactivity on target genes. Through blocking oncogenic activity of the non-canonical NF-κB signaling pathway in colorectal cancer or B lymphoma, the inhibitor efficiently exerted

SUBMITTER: Li C 

PROVIDER: S-EPMC11997474 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature