Abstract
Thioredoxin plays a crucial role in a wide number of physiological processes, which span from reduction of nucleotides to deoxyriboucleotides to the detoxification from xenobiotics, oxidants and radicals. The redox function of Thioredoxin is critically dependent on the enzyme Thioredoxin NADPH Reductase (TrxR). In view of its indirect involvement in the above mentioned physio/pathological processes, inhibition of TrxR is an important clinical goal. As a general rule, the affinities and mechanisms of binding of TrxR inhibitors to the target enzyme are known with scarce precision and conflicting results abound in the literature. A relevant analysis of published results as well as the experimental procedures is therefore needed, also in view of the critical interest of TrxR inhibitors. We review the inhibitors of TrxR and related flavoreductases and the classical treatment of reversible, competitive, non competitive and uncompetitive inhibition with respect to TrxR, and in some cases we are able to reconcile contradictory results generated by oversimplified data analysis.
Keywords: Thioredoxin reductase, mechanism of inhibition, competitive inhibitor, uncompetitive inhibitor, irreversible inhibitor, suicide substrates, pseudo-irreversible inhibition, double-substrate enzyme.
Current Protein & Peptide Science
Title:Thioredoxin Reductase and its Inhibitors
Volume: 15 Issue: 6
Author(s): Fulvio Saccoccia, Francesco Angelucci, Giovanna Boumis, Daniela Carotti, Gianni Desiato, Adriana E. Miele and Andrea Bellelli
Affiliation:
Keywords: Thioredoxin reductase, mechanism of inhibition, competitive inhibitor, uncompetitive inhibitor, irreversible inhibitor, suicide substrates, pseudo-irreversible inhibition, double-substrate enzyme.
Abstract: Thioredoxin plays a crucial role in a wide number of physiological processes, which span from reduction of nucleotides to deoxyriboucleotides to the detoxification from xenobiotics, oxidants and radicals. The redox function of Thioredoxin is critically dependent on the enzyme Thioredoxin NADPH Reductase (TrxR). In view of its indirect involvement in the above mentioned physio/pathological processes, inhibition of TrxR is an important clinical goal. As a general rule, the affinities and mechanisms of binding of TrxR inhibitors to the target enzyme are known with scarce precision and conflicting results abound in the literature. A relevant analysis of published results as well as the experimental procedures is therefore needed, also in view of the critical interest of TrxR inhibitors. We review the inhibitors of TrxR and related flavoreductases and the classical treatment of reversible, competitive, non competitive and uncompetitive inhibition with respect to TrxR, and in some cases we are able to reconcile contradictory results generated by oversimplified data analysis.
Export Options
About this article
Cite this article as:
Saccoccia Fulvio, Angelucci Francesco, Boumis Giovanna, Carotti Daniela, Desiato Gianni, Miele E. Adriana and Bellelli Andrea, Thioredoxin Reductase and its Inhibitors, Current Protein & Peptide Science 2014; 15 (6) . https://dx.doi.org/10.2174/1389203715666140530091910
DOI https://dx.doi.org/10.2174/1389203715666140530091910 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
- 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
Related Articles
-
Anticancer α-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes
Current Protein & Peptide Science HDAC Inhibitors as Novel Anti-Cancer Therapeutics
Recent Patents on Anti-Cancer Drug Discovery ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development
Current Pharmaceutical Design Biosafety of Lentiviral Vectors
Current Gene Therapy Toward Integrase Defective Lentiviral Vectors for Genetic Immunization
Current HIV Research Bone Disruption and Environmental Pollutants
Endocrine, Metabolic & Immune Disorders - Drug Targets Synthesis and In-Vitro Antitumor Activity of Selected 7-Fluoro-6-(4-methyl-1-piperazinyl)-2-(thiosubstituted)-4(3H)-quinazolinones
Letters in Organic Chemistry Daidzein and its Effects on Brain
Current Medicinal Chemistry Physiology and Therapeutics of Vascular Endothelial Growth Factor in Tumor Immunosuppression
Current Molecular Medicine E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets
Current Cancer Drug Targets A Medicinal Mushroom: Phellinus Linteus
Current Medicinal Chemistry Placental Drug Transporters
Current Drug Metabolism BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus
Current Molecular Medicine VEGF Signal System: The Application of Antiangiogenesis
Current Medicinal Chemistry Bioluminescence Imaging in Rodents: When Light Illuminates Cancer Research
Current Molecular Imaging (Discontinued) A Phosphoproteomics Approach to Identify Candidate Kinase Inhibitor Pathway Targets in Lymphoma-Like Primary Cell Lines
Current Drug Discovery Technologies Estrone Specific Molecularly Imprinted Polymeric Nanospheres: Synthesis, Characterization and Applications for Electrochemical Sensor Development
Combinatorial Chemistry & High Throughput Screening Implications of RNA Helicases in HIV-1 Replication: Possible Roles in Latency
Current HIV Research Biophysical Characterization of Glycodendrimers As Nano-carriers for HIV Peptides
Current Medicinal Chemistry Cancer “Stemness”- Regulating MicroRNAs: Role, Mechanisms and Therapeutic Potential
Current Drug Targets