Small molecule nf-kb pathway inhibitors in clinic

Abstract

Nuclear factor kappa B (NF-kB) signaling is implicated in all major human chronic diseases, with its role in transcription of hundreds of gene well established in the literature. This has propelled research into targeting the NF-kB pathways for modulating expression of those genes and the diseases mediated by them. In-spite of the critical, but often promiscuous role played by this pathway and the inhibition causing adverse drug reaction, currently many biologics, macromolecules, and small molecules that modulate this pathway are in the market or in clinical trials. Furthermore, many marketed drugs that were later found to also have NF-kB targeting activity were repurposed for new therapeutic interventions. Despite the rising importance of biologics in drug discovery, small molecules got around 76% of US-FDA (Food and Drug Administration-US) approval in the last decade. This encouraged us to review information regarding clinically relevant small molecule inhibitors of the NF-kB pathway from cell surface receptor stimulation to nuclear signaling. We have also highlighted the underexplored targets in this pathway that have potential to succeed in clinic.