NF-κBs are homo- or heterodimers of the structurally related subunits p65 (RelA), RelB, cRel, p50 and p52. NF-κB plays a key role in regulating the immune response to infection. NFκBs control the transcription of hundreds of genes, often encoding for proteins involved in immune regulation. It is also important for cell survival, differentiation and proliferation of non-immune cells.
BAY 11-7082 is a κB kinase (IKK) inhibitor wiht anticancer, neuroprotective, and anti-inflammatory effects. It strongly suppressed the production of nitric oxide, prostaglandin E2, and TNF–α. This compound reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events. In addition, it also suppressed the translocation and activation of AP-1, IRF3, and STAT1. It is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs.
Furthermore, BAY–11-7082 inhibits the proliferation and induces the apoptosis of U266 cells through inhibiting NF-κB pathway. Additionally, BAY-11-7082 can inhibit U266 cell proliferation, reduce cell viability and release IL-6. It can also induce increased proportion of apoptosis and increased expression of apoptosis-related protein. In the regulation of NF-κB pathway, it can decrease p65, p50 and IKKβ mRNA expressions, and reduce p65 and p-IKKβ activation. Besides, BAY 11-7082 was able to ameliorate experimental diabetic neuropathy by modulating neuroinflammation and improving antioxidant defence. It alleviated abnormal sensory responses and deficits in nerve functions. BAY 11-7082 also ameliorated the increase in expression of NF-κB, IκB and p-IκB. It curbed down the levels of IL-6, TNF-α, COX-2 and iNOS in the sciatic nerve.