Product Feature - NFκB Signalling

NF-κB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types. It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immune response to infection. In unstimulated cells NF-κB dimers are sequestered inactively in the cytoplasm by a protein complex called inhibitor of kappa B (IκB). IκB inactivates NF-κB by masking the nuclear localisation signals (NLS).

Activation of NF-κB occurs via degradation of IκB, a process that is initiated by its phosphorylation by IκB kinase (IKK). Phosphorylated IκB becomes dissociated from NF-κB, unmasking the NLS. Phosphorylation also results in IκB ubiquitination and targeting to the proteasome. NF-κB can now enter the nucleus and regulate gene expression. NF-κB turns on expression of IκB forming a negative feedback loop.

Key IKK inhibitors available from Tocris include:

Selective inhibitor of IKK
2539 l IKK 16
Inhibits TNFα-stimulated IκB degradation and expression of adhesion molecules E-selectin, ICAM and VCAM (IC₅₀ values are 1.0, 0.5, 0.3 and 0.3 μM respectively). In vivo, inhibits LPS-induced TNF-α release and neutrophil extravasion in thioglycollate-induced peritonitis.

Inhibitor of IKK-2
2611 l IMD 0354
Blocks NF-κB nuclear translocation. Attenuates myocardial ischaemia/reperfusion injury by decreasing expression of adhesion molecules ICAM-1 and P-selectin and inhibiting cytokine and chemokine production in cardiomyocytes. Induces G₀/G₁ cell cycle arrest and apoptosis in HMC-1 and breast cancer cells.

Potent, selective inhibitor of IKK-2
2559 l TPCA-1
Displays > 22-fold selectivity over IKK-1 and > 550-fold selectivity over other kinases and enzymes. Inhibits production of pro-inflammatory cytokines in vitro and in vivo and inhibits NF-κB nuclear localisation. Reduces the severity and onset of collagen-induced arthritis; anti-inflammatory.

NF-κB and Cancer

NF-κB regulates the genes involved in cell proliferation and cell survival and has been found to be misregulated (constitutively active) in many human tumours. Constitutive activation of NF-κB can result from a mutation in NF-κB itself or in genes that control its activity e.g. IκB. Blocking NF-κB activation can stop tumour cell proliferation and induce cell death, therefore inhibitors of IKK are therefore promising targets for anticancer therapies.

www.tocris.com | About Tocris Bioscience | Company History | Contact Us

Highlights over 150 new products

More NF-κB Signalling Compounds

NF-κB signalling and Cancer

Okamoto et al review NF-κB
signalling and carcinogenesis (more)