A naturally derived small molecule NDSM253 inhibits IKK1 to suppress inflammation response and promote bone healing after fracture.

ABSTRACT: Bone fracture induces an acute inflammatory response in the resident and peripheral monocyte/macrophage cells. Excessive amounts of proinflammatory cytokines can cause severe tissue damage and inhibit bone healing. The proinflammatory cytokine genes are mainly controlled by TLR4/NF-κB (Toll-like receptor 4/Nuclear factor κB). Thus, targeting the molecules in this signaling pathway to decrease the expression of proinflammatory cytokines is an effective strategy to inhibit the inflammatory response. Herein, we identified a naturally derived small molecule NDSM253 that specifically inhibited IKKα (Inhibitor of NF-κB kinase subunit-alpha), a critical component of TLR4/NF-κB signaling. Biochemically, NDMS253 decreased phosphorylation of IκB (Inhibitor of NF-κB), thereby increasing the binding o

SUBMITTER: Shen L 

PROVIDER: S-EPMC7847520 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature