Progress Towards the Development of Anti-Inflammatory Inhibitors of IKKβ

被引：26

作者：

Bamborough, Paul ^{[1
]}

Callahan, James F. ^{[2
]}

Christopher, John A. ^{[1
]}

Kerns, Jeffrey K. ^{[2
]}

Liddle, John ^{[1
]}

Miller, David D. ^{[1
]}

Morse, Mary A. ^{[1
]}

Rumsey, William L. ^{[2
]}

Williamson, Rick ^{[1
]}

机构：

[1] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England

[2] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2009年 / 9卷 / 07期

关键词：

I-kappa B kinase inhibitors; IKK; IKK beta; NF-kappa B; inflammation; KAPPA-B-KINASE; HIGHLY SELECTIVE INHIBITOR; ADENOVIRAL-MEDIATED DELIVERY; COLLAGEN-INDUCED ARTHRITIS; HIT-TO-LEAD; CIGARETTE-SMOKE; DEPENDENT TRANSCRIPTION; INFLAMMATORY CYTOKINE; AIRWAY INFLAMMATION; THERAPEUTIC TARGET;

D O I：

10.2174/156802609789007336

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The I B kinases (IKKs) are essential components of the signaling pathway by which the NF-kappa B p50/RelA transcription factor is activated in response to pro-inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha). NF-kappa B 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 (R Lambda), 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 IKK beta (IKK2), the most widely studied of the IKKs.

引用

页码：623 / 639

页数：17

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