Inhibitors of AP-1 and NF-kappa B 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-kappa B) is essential for the transcriptional regulation of the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF alpha, 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, TNF alpha, and GM-CSF. During the last few years, several groups have developed inhibitors of AP-1, NF-kappa B or both, and NFAT. This review article presents the recent progress in the development of inhibitors for AP-1, NF-kappa B, and NFAT mediated transcriptional activation.
Palanki
Moorthy S S
MS
Department of Medicinal Chemistry, Celgene Signal Research Division, 5555 Oberlin Drive, San Diego, CA 92121, USA. MPalanki@signalpharm.com
D001327:Autoimmune Diseases / Q000188:drug therapy*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*
D016328:NF-kappa B; D018808:Transcription Factor AP-1