Nuclear factor-κB (NF-κB), a collective term for a family of transcription factors, includes five subunits: NF-κB1 (p50/p105), NF-κB2 (p52/p100), p65 (RelA), RelB, and c-Rel. The homodimers or heterodimers formed by two subunits bind to specific sequences known as the κB site on their target genes for DNA interaction and transcriptional activation. How NF-κB selectively recognizes a small subset of relevant κB sites from the large excess of potential binding sites is a critical step for stimulus-specific gene transcription (The fine-tuning of the NF-B DNA binding activity).While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase(IKK). IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteasome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such as coactivators and RNA polymerase, which transcribe downstream DNA into mRNA. A large array of genes involved in different processes of the immune and inflammatory responses, such as TNF-α, IL-1β, IL-6, and IL-8, chemokines, adhesion molecules, clone stimulating factors, is mediated by NF-κB. In TNF-α–induced apoptosis, TRAF1, TRAF2, XIAP, c-IAP1, and c-IAP2 were identified as gene targets of NF-kB transcriptional activity.

NF-κB Signaling Compound Library from TargetMol, a unique collection of 729 small molecules targeting NF-κB signaling, can be used for research in NF-κB signaling and high throughput screening and high content screening.