Inhibitors of AP-1 and NF-κB mediated transcriptional activation:: Therapeutic potential in autoimmune diseases and structural diversity

Cytokines and chemokines play a very important role in a number of inflammatory diseases. In activated T cells, transcription factors such as the activator protein-1 (AP-1) regulate IL-2 production and production of matrix metalloproteinases, the nuclear factor kappa B (NF-kappaB) is essential for the transcriptional regulation of the proinflammatory cytokines IL-1, IL-6, IL-8 and TNFalpha, and nuclear factor of activated T-cells (NFAT) is required for the transcriptional regulation of IL-2, IL-3, IL-4, IL-5, IL-8, IL-13, TNFalpha, and GM-CSF. During the last few years, several groups have developed inhibitors of AP-1, NF-kappaB or both, and NFAT. This review article presents the recent progress in the development of inhibitors for AP-1, NF-kappaB, and NFAT mediated transcriptional activation.