Figure 1

Canonical and non canonical NF-kB pathways and related drugs inhibition. The canonical pathway induces activation of IkB-bound NF-κB species (such as relA/p50 or cRel/p50) through activation of an upstream multimeric IKK complex, formed by IKKα, IKKβ, and IKKγ or NEMO; this activation results in the phosphorylation (P) of IkBα, its ubiquitylation (Ub) and subsequent degradation by the 26S proteasome. Release of the NF-κB complex allows it to relocate to the nucleus. The non canonical pathway depends on activation of IKKα dimers only. Four drugs that are used to block NF-κB pathways with different mechanism are represented. Bortezomib is a proteasome inhibitor that blocks the degradation of IkBα; curcumin and BMS-345541 inhibit IKK complex formation (both heterodimeric that omodimeric forms); NBD peptide targets the NBD-NEMO interaction. The first three compounds block both canonical and non canonical signaling, whereas NBD peptide blocks the canonical pathway only.