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Inhibiting NF-kappaB activation by small molecules as a therapeutic strategy Gupta SC; Sundaram C; Reuter S; Aggarwal BBBiochim Biophys Acta 2010[Oct]; 1799 (10-12): 775-87Because nuclear factor-kappaB (NF-kappaB) is a ubiquitously expressed proinflammatory transcription factor that regulates the expression of over 500 genes involved in cellular transformation, survival, proliferation, invasion, angiogenesis, metastasis, and inflammation, the NF-kappaB signaling pathway has become a potential target for pharmacological intervention. A wide variety of agents can activate NF-kappaB through canonical and noncanonical pathways. Canonical pathway involves various steps including the phosphorylation, ubiquitination, and degradation of the inhibitor of NF-kappaB (IkappaBalpha), which leads to the nuclear translocation of the p50-p65 subunits of NF-kappaB followed by p65 phosphorylation, acetylation and methylation, DNA binding, and gene transcription. Thus, agents that can inhibit protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and DNA binding steps have been identified as NF-kappaB inhibitors. Because of the critical role of NF-kappaB in cancer and various chronic diseases, numerous inhibitors of NF-kappaB have been identified. In this review, however, we describe only small molecules that suppress NF-kappaB activation, and the mechanism by which they block this pathway.|Animals[MESH]|Cell Proliferation/drug effects[MESH]|Cell Survival/drug effects[MESH]|Cell Transformation, Neoplastic/drug effects/metabolism[MESH]|Gene Expression Regulation/drug effects[MESH]|Humans[MESH]|I-kappa B Kinase/antagonists & inhibitors/metabolism[MESH]|Inflammation/drug therapy/metabolism/pathology[MESH]|NF-kappa B/*antagonists & inhibitors/*chemistry/*metabolism[MESH]|Neoplasm Invasiveness[MESH]|Neoplasm Metastasis[MESH]|Neoplasms/drug therapy/metabolism/pathology[MESH]|Neovascularization, Physiologic/drug effects[MESH]|Phosphorylation/drug effects[MESH]|Signal Transduction/drug effects[MESH] |
