Abstract
The development of inflammatory immune response is related to an activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) 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-κB 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-κB 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- κB 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.
Keywords: Ataxia-telangiectasia (A-T) mutated kinase, IκB kinase, Neddylation, NF-κB pathway, Reactive oxygen species, Redox sensors, Small molecule inhibitors.
Current Topics in Medicinal Chemistry
Title:Kinase Inhibitors with Redox and Anti-inflammatory Activities
Volume: 15 Issue: 9
Author(s): Nina Ivanovska, Luciano Saso and Petya Dimitrov
Affiliation:
Keywords: Ataxia-telangiectasia (A-T) mutated kinase, IκB kinase, Neddylation, NF-κB pathway, Reactive oxygen species, Redox sensors, Small molecule inhibitors.
Abstract: The development of inflammatory immune response is related to an activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) 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-κB 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-κB 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- κB 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.
Export Options
About this article
Cite this article as:
Ivanovska Nina, Saso Luciano and Dimitrov Petya, Kinase Inhibitors with Redox and Anti-inflammatory Activities, Current Topics in Medicinal Chemistry 2015; 15 (9) . https://dx.doi.org/10.2174/1568026615666150220115838
DOI https://dx.doi.org/10.2174/1568026615666150220115838 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Epigenetic Regulation of Cytochrome P450 Enzymes and Clinical Implication
Current Drug Metabolism Recent Progress on Antifungal Drug Development
Current Pharmaceutical Biotechnology The Validation Path of Hypoxia PET Imaging: Focus on Brain Tumours
Current Medicinal Chemistry Alternative Splice Variants of Survivin as Potential Targets in Cancer
Current Drug Discovery Technologies Cancer Therapy By Targeting Hypoxia-Inducible Factor-1
Current Cancer Drug Targets Exploiting Apoptosis Pathways for the Treatment of Pancreatic Cancer
Current Signal Transduction Therapy Dendritoma Vaccine for Cancer: A Hopeful Approach
Current Cancer Therapy Reviews Dihydromyricetin Reduces TGF-β Via P53 Activation-dependent Mechanism in Hepatocellular Carcinoma HepG2 Cells
Protein & Peptide Letters Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications
Current Pharmaceutical Design CYP4 Enzymes As Potential Drug Targets: Focus on Enzyme Multiplicity, Inducers and Inhibitors, and Therapeutic Modulation of 20- Hydroxyeicosatetraenoic Acid (20-HETE) Synthase and Fatty Acid ω- Hydroxylase Activities
Current Topics in Medicinal Chemistry Recent Advances and Strategies in Tumor Vasculature Targeted Nano-Drug Delivery Systems
Current Pharmaceutical Design Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?
Current Pharmacogenomics and Personalized Medicine Genetic Variants in Genes Involved in Mechanisms of Chemoresistance to Anticancer Drugs
Current Cancer Drug Targets New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Ectonucleotidases and Nucleotide/Nucleoside Transporters as Pharmacological Targets for Neurological Disorders
CNS & Neurological Disorders - Drug Targets Feud or Friend? The Role of the miR-17-92 Cluster in Tumorigenesis
Current Genomics p53 Regulation of Energy Metabolism and Mitochondria Regulation of p53 in Cancer Cells: An Insight into the Role of Manganese Superoxide Dismutase
Current Pharmaceutical Biotechnology Multifunctional Proteins in Tumorigenesis: Aminoacyl-tRNA Synthetases and Translational Components
Current Proteomics Mechanisms of Intrinsic and Acquired Resistance to EGFR Inhibitors
Current Cancer Therapy Reviews Emerging Therapeutic Targets and Agents for Glioblastoma Migrating Cells
Anti-Cancer Agents in Medicinal Chemistry