Inhibitory kappa B Kinases as targets for pharmacological regulation.
paper
Cited
Public
Unavailable
- Authors
- Gamble, Carly; McIntosh, Kathryn; Scott, Rebecca; Ho, Ka Ho; Plevin, Robin; Paul, Andrew
- Year
- 2012
- Journal
- British journal of pharmacology
- PMID
- 21797846
- DOI
- 10.1111/j.1476-5381.2011.01608.x
- PMCID
- PMC3312479
The inhibitory kappa B kinases (IKKs) are well recognized as key regulators of the nuclear factor kappa B (NF-κB) cascade and as such represent a point of convergence for many extracellular agents that activate this pathway. The IKKs generally serve to transduce pro-inflammatory and growth stimulating signals that contribute to major cellular processes but also play a key role in the pathogenesis of a number of human diseases. Therefore, the catalytic IKKs represent attractive targets for intervention with small molecule kinase inhibitors. IKK isoforms are assembled as variable multi-subunit IKK complexes that regulate not only NF-κB dimers, but also protein substrates out-with this cascade. Consequently, close consideration of how these individual complexes transduce extracellular signals and more importantly what impact small molecule inhibitors of the IKKs have on functional outcomes are demanded. A number of adenosine triphosphate (ATP)-competitive IKKβ-selective inhibitors have been developed but have demonstrated a lack of activity against IKKα. A number of these chemicals have also exhibited detrimental outcomes such as cellular toxicity and immuno-suppression. The impact of small molecule inhibitors of IKK catalytic activity will therefore be reappraised, examining the advantages and potential disadvantages to this type of intervention strategy in the treatment of diseases such as arthritis, intestinal inflammation and cancer. Furthermore, we will outline some emerging strategies, particularly the disruption of protein-protein interactions within the IKK complex, as an alternative route towards the development of novel pharmacological agents. Whether these alternatives may negate the limitations of ATP-competitive molecules and potentially avoid the issues of toxicity will be discussed.
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| Anticancer effects of marine compounds blocking the nuclear factor kappa B signaling pathway. | Wei J et al. | — | 2022 | → |
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| Emodin Reverses Gemcitabine Resistance of Pancreatic Cancer Cell Lines Through Inhibition of IKKβ/NF-κB Signaling Pathway. | Tong H et al. | — | 2020 | → |
| Gibberellin JRA-003: A Selective Inhibitor of Nuclear Translocation of IKKα. | Annand JR et al. | — | 2020 | → |
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| NF-κB inhibitor, NEMO-binding domain peptide attenuates intervertebral disc degeneration. | Glaeser JD et al. | — | 2020 | → |
| NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. | Cores Á et al. | — | 2020 | → |
| TGF-β/PI3K/AKT/mTOR/NF-kB pathway. Clinicopathological features in prostate cancer. | Torrealba N et al. | — | 2020 | → |
| Therapeutic effects of IkB kinase inhibitor during systemic inflammation. | Amaro-Leal  et al. | — | 2020 | → |
| Thiazolidine-2,4-dione-based irreversible allosteric IKK-β kinase inhibitors: Optimization into in vivo active anti-inflammatory agents. | Elkamhawy A et al. | — | 2020 | → |
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| Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets. | Paul A et al. | — | 2018 | → |
| NFKB1 and Cancer: Friend or Foe? | Concetti J et al. | — | 2018 | → |
| NF-κB Activation in Lymphoid Malignancies: Genetics, Signaling, and Targeted Therapy. | Grondona P et al. | — | 2018 | → |
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| 4-Hydroxy-<i>N</i>-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a novel inhibitor of the canonical NF-κB cascade. | Pippione AC et al. | — | 2017 | → |
| Chalcone: A Privileged Structure in Medicinal Chemistry. | Zhuang C et al. | — | 2017 | → |
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| Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity. | Begalli F et al. | — | 2017 | → |
| Diallyl Disulfide (DADS), a Constituent of Garlic, Inactivates NF-κB and Prevents Colitis-Induced Colorectal Cancer by Inhibiting GSK-3β. | Saud SM et al. | — | 2016 | → |
| Inhibition of IKKβ Reduces Ethanol Consumption in C57BL/6J Mice. | Truitt JM et al. | — | 2016 | → |
| Mechanisms of NF-κB deregulation in lymphoid malignancies. | Krappmann D et al. | — | 2016 | → |
| Targeting IκB Kinase β/NF-κB Signaling in Human Prostate Cancer by a Novel IκB Kinase β Inhibitor CmpdA. | Zhang Y et al. | — | 2016 | → |
| The Th1/Th2 paradigm in lambda cyhalothrin-induced spleen toxicity: The role of thymoquinone. | Hussein MM et al. | — | 2016 | → |
| Apigenin blocks IKKα activation and suppresses prostate cancer progression. | Shukla S et al. | — | 2015 | → |
| Diverse Molecular Targets for Chalcones with Varied Bioactivities. | Zhou B et al. | — | 2015 | → |
| EcSTAT3ic about K63-Linked Ubiquitylation of IKKβ. | Carrano AC | — | 2015 | → |
| Inhibition of IκB kinase (IKK) protects against peripheral nerve dysfunction of experimental diabetes. | Negi G et al. | — | 2015 | → |
| Local and Systemic IKKε and NF-κB Signaling Associated with Sjögren's Syndrome Immunopathogenesis. | Chen W et al. | — | 2015 | → |
| Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. | Tebay LE et al. | — | 2015 | → |
| Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes. | Oguiza A et al. | — | 2015 | → |
| Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans. | Blednov YA et al. | — | 2015 | → |
| Targeting the NFκB signaling pathways for breast cancer prevention and therapy. | Wang W et al. | — | 2015 | → |
| URGCP promotes non-small cell lung cancer invasiveness by activating the NF-κB-MMP-9 pathway. | Cai J et al. | — | 2015 | → |
| A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma. | Habineza Ndikuyeze G et al. | — | 2014 | → |
| Identification of plumericin as a potent new inhibitor of the NF-κB pathway with anti-inflammatory activity in vitro and in vivo. | Fakhrudin N et al. | — | 2014 | → |
| Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: a role for hypothalamic inflammation. | Ying Z et al. | — | 2014 | → |
| Polyphenol-rich blackcurrant extract prevents inflammation in diet-induced obese mice. | Benn T et al. | — | 2014 | → |
| The role of IKKβ in Venezuelan equine encephalitis virus infection. | Amaya M et al. | — | 2014 | → |
| The role of the IKK complex in viral infections. | Amaya M et al. | — | 2014 | → |
| Insight into the intermolecular recognition mechanism between Keap1 and IKKβ combining homology modelling, protein-protein docking, molecular dynamics simulations and virtual alanine mutation. | Jiang ZY et al. | — | 2013 | → |
| Moving to the core: spatiotemporal analysis of Forkhead box O (FOXO) and nuclear factor-κB (NF-κB) nuclear translocation. | Zanella F et al. | — | 2013 | → |
| Targeting the NF-κB and mTOR pathways with a quinoxaline urea analog that inhibits IKKβ for pancreas cancer therapy. | Radhakrishnan P et al. | — | 2013 | → |
| Targeting the NF-κB pathway in cancer therapy. | Erstad DJ et al. | — | 2013 | → |
| Towards the small and the beautiful: a small dibromotyrosine derivative from Pseudoceratina sp. sponge exhibits potent apoptotic effect through targeting IKK/NFκB signaling pathway. | Su JH et al. | — | 2013 | → |
| The taming of the NF-κB: PP4R1 navigates while PP4c dephosphorylates. | Tikhonova A et al. | — | 2012 | → |