Title:NF-κB-IKKβ Pathway as a Target for Drug Development: Realities, Challenges and Perspectives
Volume: 19
Issue: 16
Author(s): Rosana H.C.N. Freitas and Carlos A.M. Fraga*
Affiliation:
- LASSBio, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro,Brazil
Keywords:
NF-κB, IKKβ, inflammation, cancer, proteasome inhibitor, N-acylhydrazone.
Abstract: Background: Nuclear factor κB (NF-κB) comprises a family of proteins that act as transcription
factors promoting the expression of many genes. Activation of NF-κB biochemical cascades
is associated with the regulation of innate and adaptive immune responses and inflammation, among
other physiological responses. However, genetic abnormalities and continuous stimulation of the NF-
κB-IKKβ pathway are directly related to many types of inflammatory and autoimmune diseases, as
well as to the genesis and survival of tumor cells.
Objectives: Inhibition of the NF-κB-IKKβ cascade can be considered an attractive therapeutic method
for the genesis of new prototypes to combat these chronic multifactorial diseases.
Results: This review describes some prototypes and drugs that act to inhibit the NF-κB-IKKβ pathway,
highlighting the realities, challenges and perspectives for therapeutic use.
Conclusion: Although only proteasome inhibitors, such as bortezomib and carfilzomib, are a reality as
therapeutically useful drugs among the known modulators of possible targets in the NF-κB-IKKβ
pathway, some other prototypes described as IKKβ inhibitors have entered clinical stages as drug candidates
for the control of inflammatory diseases. It is important to note that some classical drugs available
on the pharmaceutical market, such as acetylsalicylic acid, were also described more recently as
NF-κB pathway modulators as IKKβ inhibitors.
