Kinase Inhibitors with Redox and Anti-inflammatory Activities

被引:4
|
作者
Ivanovska, Nina [1 ]
Saso, Luciano [2 ]
Dimitrova, Petya [1 ]
机构
[1] Bulgarian Acad Sci, Dept Immunol, Inst Microbiol, 26 Georgi Bonchev Str, BU-1113 Sofia, Bulgaria
[2] Dept Physiol & Pharmacol Vittorio Erspamer, I-00185 Rome, Italy
关键词
Ataxia-telangiectasia (A-T) mutated kinase; I kappa B kinase; Neddylation; NF-kappa B pathway; Reactive oxygen species; Redox sensors; Small molecule inhibitors; NF-KAPPA-B; PROINFLAMMATORY CYTOKINE PRODUCTION; COLLAGEN-INDUCED ARTHRITIS; SEVERE LIVER DEGENERATION; ATM PROTEIN-KINASE; ATAXIA-TELANGIECTASIA; IKK-BETA; NEDD8-ACTIVATING ENZYME; OXIDATIVE STRESS; BAY; 11-7082;
D O I
10.2174/1568026615666150220115838
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The development of inflammatory immune response is related to an activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling. The intracellular molecules from this pathway are sensitive to the alterations in the microenvironment. The changes in cellular redox state, proliferation, gene expression pattern and genomic stability during inflammation induce the activation of non-canonical and atypical NK-kappa B signaling increasing the crosstalk with molecules involved in neddylation, cell cycle checkpoints regulation and DNA repair. This review article describes the reactive oxygen species (ROS)-sensitive kinases from the NF-kappa B pathway and presents the effects of their suppression by small kinase inhibitors. It illustrates that selective targeting of the redox sensor molecules from the inflammatory NK-kappa B cascades can influence cell survival and metabolism as well. We think that this issue is important when evaluating the drug efficacy in clinical studies and their side effects.
引用
收藏
页码:872 / 885
页数:14
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