Merck UK - Calbiochem - Inhibitors: Other

		Technical Resources

		Technical Information

		Calbiochem Information

		Inhibitor Resource

		Other Inhibitors

		Adenylate Cyclase
		ACE
		ATPase
		FTase and GGTase
		Glycoprotein Processing and Trafficking
		Heat Shock Protein
		KSP/Eg5
		Mitochondrial Function
		NF-kB Activation
		Phosphodiesterase
		Plasminogen Activator
		Protein Synthesis
		Sonic Hedgehog Signaling
		STAT3
		Protein Methtyltransferase, Stem Cell Purification, Tautomerase

Other Inhibitors: NF-kB Activation Inhibitors

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Inhibitors | Related Resources

NF-kB, a eukaryotic transcription factor plays an important role in inflammation, autoimmune response, cell proliferation, and apoptosis by regulating the expression of genes involved in these processes. It consists of homo- or heterodimers of different subunits, which belong to a family of Rel/NF-kB proteins. Five different Rel proteins [p50, p52, p65 (Rel A), RelB, and c-Rel] have been identified thus far. The most prevalent activated form of NF-kB is a heterodimer of p50 or p52 subunit and p65, which contains transactivation domains necessary for gene induction. In unstimulated cells, NF-kB is sequestered in the cytoplasm in an inactive form, bound to regulatory proteins called inhibitors of kB (IkB), of which IkBa and IkBb are considered to be the most important. IkBa is associated with transient NF-kB activation, whereas IkBb is involved in sustained activation.

The activity of NF-kB is tightly regulated by interaction with inhibitory IkB proteins. In most resting cells, NF-kB is sequestered in the cytoplasm in an inactive form associated with inhibitory molecules, such as IkBa, IkBb, IkBh, p105, and p100. This interaction blocks the ability of NF-kB to bind to DNA and results in the NF-kB complex being primarily localized to the cytoplasm due to a strong nuclear export signal in IkBa.

Stimulation of cells by inflammatory cytokines, UV light, or reactive oxygen species leads to the rapid phosphorylation, ubiquitination, and ultimately proteolytic degradation of IkB, which frees NF-kB from the NF-kB-IkB complex. NF-kB then translocates to the nucleus where it binds to kB enhancer elements of proinflammatory target genes to induce transcription. NF-kB is highly activated at sites of inflammation in diverse diseases and induces transcription of pro-inflammatory cytokines, chemokines, adhesion molecules, MMPs, COX-2, and inducible nitric oxide (iNOS). Hence, NF-kB has been considered as a desirable target for therapy in various inflammatory diseases. In most cancer cells, NF-kB is constitutively active and resides in the nucleus. In some cases, this may be due to chronic stimulation of the IKK pathway, while in others the gene encoding IkBa may be defective. Such continuous nuclear NF-kB activity not only protects cancer cells from apoptotic cell death, but may even enhance their growth activity. Designing antitumor agents to block NF-kB activity or to increase sensitivity to conventional chemotherapy may have great therapeutic value.