Small Molecule Inhibitors of NF-κB and JAK/STAT Signal Transduction Pathways as Promising Anti-Inflammatory Therapeutics

In the current review, we discuss the role of NF-κB and JAK/STAT signaling pathways and their small molecule regulators in the therapy of inflammatory diseases. Considering potential harmful effects directly assigned to the COX-2 inhibition, novel therapeutically-relevant biological targets such as NF-κB and JAK/STAT signaling pathways have received a growing attention. Here we summarize recent progress in the identification and development of novel, clinically approved or evaluated small molecule regulators of these signaling cascades as promising anti-inflammatory therapeutics. In addition, we illustrate key structural modifications and bioisosteric transformations among these inhibitors to provide a helpful basis for further development of novel small molecule anti-inflammatory agents.