Abstract
Disrupted kynurenine pathway (KP) metabolism has been implicated in the progression of neurodegenerative disease, psychiatric disorders and cancer. Modulation of enzyme activity along this pathway may therefore offer potential new therapeutic strategies for these conditions. Considering their prominent positions in the KP, the enzymes indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase and kynurenine aminotransferase, appear the most attractive targets. Already, increasing interest in this pathway has led to the identification of a number of potent and selective enzyme inhibitors with promising pre-clinical data and the elucidation of several enzyme crystal structures provides scope to rationalize the molecular mechanisms of inhibitor activity. The field seems poised to yield one or more inhibitors that should find clinical utility.
Keywords: Kynurenine pathway, neurodegeneration, cancer, indoleamine 2, 3-dioxygenase, kynurenine 3- monooxygenase, enzyme inhibitors.
Current Medicinal Chemistry
Title:Major Developments in the Design of Inhibitors along the Kynurenine Pathway
Volume: 24 Issue: 23
Author(s): Kelly R. Jacobs, Gloria Castellano-Gonzalez , Gilles J. Guillemin *David B. Lovejoy *
Affiliation:
- Department of Biomedical Research, Faculty of Medicine and Health Science, Macquarie University, 2 Technology Place, Sydney,Australia
- Department of Biomedical Research, Faculty of Medicine and Health Science, Macquarie University, 2 Technology Place, Sydney,Australia
Keywords: Kynurenine pathway, neurodegeneration, cancer, indoleamine 2, 3-dioxygenase, kynurenine 3- monooxygenase, enzyme inhibitors.
Abstract: Disrupted kynurenine pathway (KP) metabolism has been implicated in the progression of neurodegenerative disease, psychiatric disorders and cancer. Modulation of enzyme activity along this pathway may therefore offer potential new therapeutic strategies for these conditions. Considering their prominent positions in the KP, the enzymes indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase and kynurenine aminotransferase, appear the most attractive targets. Already, increasing interest in this pathway has led to the identification of a number of potent and selective enzyme inhibitors with promising pre-clinical data and the elucidation of several enzyme crystal structures provides scope to rationalize the molecular mechanisms of inhibitor activity. The field seems poised to yield one or more inhibitors that should find clinical utility.
Export Options
About this article
Cite this article as:
Jacobs R. Kelly, Castellano-Gonzalez Gloria , Guillemin J. Gilles*, Lovejoy B. David*, Major Developments in the Design of Inhibitors along the Kynurenine Pathway, Current Medicinal Chemistry 2017; 24 (23) . https://dx.doi.org/10.2174/0929867324666170502123114
DOI https://dx.doi.org/10.2174/0929867324666170502123114 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Safety of Systemic Biologic Agents in the Treatment of Non-malignant Skin Disorders
Current Drug Safety A Review of Natural and Modified Betulinic, Ursolic and Echinocystic Acid Derivatives as Potential Antitumor and Anti-HIV Agents
Mini-Reviews in Medicinal Chemistry Neoadjuvant Chemotherapy Before Radical Cystectomy: Why We Must Adhere?
Current Drug Targets The Immunohistochemical Expression of the E-Cadherin, Alpha-Catenin,Beta-Catenin and Gamma Catenin Proteins in Epithelial Ovarian Tumours: Relationship with Clinicopathologic Parameters and Patient Survival
Current Women`s Health Reviews Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Heparin, Heparan Sulfate and Heparanase in Cancer: Remedy for Metastasis?
Anti-Cancer Agents in Medicinal Chemistry Breath Analysis: The Approach Towards Clinical Applications
Mini-Reviews in Medicinal Chemistry Radiolabelled Quinoline Derivaties for the PET Imaging of Peripheral Benzodiazepine Receptor
Current Medical Imaging Potential Applications of FDG-PET/CT in COPD: A Review of the Literature
Current Molecular Imaging (Discontinued) Identification of a RhoA- and SRF-Dependent Mechanism of Androgen Action that is Associated with Prostate Cancer Progression
Current Drug Targets Metals and Metal Derivatives in Medicine
Mini-Reviews in Medicinal Chemistry Cancer Control by Phytochemicals
Current Pharmaceutical Design Mucoadhesive Vaginal Drug Delivery Systems
Recent Patents on Drug Delivery & Formulation The Diversity of Epithelial Secreted Mucins
Current Organic Chemistry Angiogenesis Inhibitors and Radiation in Multimodality Cancer Therapy: Preclinical and Clinical Studies
Current Angiogenesis (Discontinued) Synthesis, Characterization and In Vitro Antiproliferative Effects of Novel 5-Amino Pyrazole Derivatives against Breast Cancer Cell Lines
Recent Patents on Anti-Cancer Drug Discovery Overcoming Drug Resistance and Treating Advanced Prostate Cancer
Current Drug Targets Natural Products: Potential for Developing Phellodendron amurense Bark Extract for Prostate Cancer Management
Mini-Reviews in Medicinal Chemistry The Effects of Insulin and Insulin-Like Growth Factors on Tumor Vascularization: New Insights of Insulin-Like Growth Factor Family in Cancer
Current Medicinal Chemistry Small Molecules as Anti-TNF Drugs
Current Medicinal Chemistry