NF-ΚB(nuclear factor-kappa B) is complex which consisted by a class of multigene family NF-κB-Rel. In vertebrates, it conclude 5 subunits: p105-p50(NF-κB1), p100-p52(NF-κB2), p65 (RelA), c-Rel and RelB. There are two major signaling pathway can active NF-ΚB (in picture 1).

The first is the classical pathway, NF-κB dimer and IκBα combined with its nuclear localization signal and DNA binding domain protein is inhibited by profilin of IκBα. Bacterial and viral infections as well as some of the ligand (TNF, IL-1, LSP, CD40L) can bind with corresponding receptors on the cells surface. Ligand bound receptor proteins can be raised to some joints receptor cytoplasmic side of the structure domain, which is capable of recruiting Iκ adapter protein kinase (IκK) binding complexes therewith. Then active IκK composite phosphorylate residue of two conserved serine of IκB. IκB is phosphorylated after will be ubiquitinated, the ultimate degradation by the 26S proteasome. The released NF-κB into the nucleus acts on the target gene.

In passing through the bypass, the binding of signaling molecules with the receptor induced NF-κB activation kinase NIK. Avtived NIK phosphorylate IκKα, and activated IκKα composite will phosphorylate P100. Phosphorylation leading to partial hydrolysis of P100 by P100 into P52, its nuclear localization signals and DNA binding domain is exposed, with the composition of the composite body into the nucleus RelB activate the site.

NF-κB is almost always expressed in all cells in the face of trauma, hypoxia, physical and chemical irritation and other stress conditions, NF-κB activation and nuclear translocation of large quantities, through the induction of various cytokines, chemokines, adhesion molecules, transcription enzymes and antimicrobial peptides, the rapid activation of the immune response, and thus play a central role in the inflammatory response link. In the past decade, researchers have done a lot of in-depth study for the role of NF-κB in cancer mechanisms. Abnormal activation of NF-κB has found in many different stages of the tumor and its development. Therefore, if the small-molecule inhibitors can be reduced NF-κB activity, these diseases will have important therapeutic implications.

In the latest article, researchers report that confirmed a complex natural product ainsliadimer A is a potent inhibitor of NF-κB signaling pathway. Ainsliadimer A selectively binds IKKα / β of 46 conserved cysteine ​​residues, inhibit their activity by allosteric effectors, thereby inhibiting the classical and non-classical NF-κB signaling pathway. Notably, ainsliadimer A can induce a variety of cancer cell death and tumor growth inhibition in vivo as well as endotoxin-mediated inflammation.

These findings not only confirm ainsliadimer A are potent IKKα / β inhibitor, also indicates ainsliadimer A can be used as lead compounds for the development of the treatment of cancer and inflammatory diseases of the drug.