NF-κB has been implicated in almost all chronic diseases, and more than 40,000 studies on NF-κB have been published with 9000 on its inhibitors. Although more than 700 different inhibitors (aspirin to IκBα super repressor) of this transcription factor have been reported, yet no NF-κB blocker has been approved for human use. Various steroids and NSAIDs have been found to block NF-κB, but their effects are highly pleiotropic. The molecules that block NF-κB activation lack specificity and thus interfere with NF-κB’s physiological roles in immunity, inflammation, and cellular homeostasis. Additionally, whether the concentrations of inhibitors used in tissue culture experiments can be applied in vivo is often unclear. Therefore, one of the major challenges facing researchers is to develop NF-κB inhibitors aimed at treating different diseases based on their ability to target specific pathways or cells, thereby avoiding the risk of undesired side effects. Future studies should also focus on validating in vitro data in vivo.
