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Progress Towards the Development of Anti-Inflammatory Inhibitors of IKKβ

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Abstract:

The IκB kinases (IKKs) are essential components of the signaling pathway by which the NF-κB p50/RelA transcription factor is activated in response to pro-inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor (TNFα). NF-κB signaling results in the expression of numerous genes involved in innate and adaptive immune responses. The pathway is also implicated in chronic inflammatory disorders including rheumatoid arthritis (RA), chronic obstructive pulmonary disorder (COPD), and asthma. Inhibition of the kinase activity of the IKKs is therefore a promising mechanism for intervention in these diseases. Here, we will review the literature describing small molecule inhibitors of IKKβ (IKK2), the most widely studied of the IKKs.

Keywords: I-kappa B kinase inhibitors; IKK; IKKβ; NF-κB; inflammation

Document Type: Research Article

DOI: https://doi.org/10.2174/156802609789007336

Affiliations: GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.

Publication date: 2009-05-01

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