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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Drug Analogs of COX-2 Selective Inhibitors Lumiracoxib and Valdecoxib Derived from in silico Search and Optimization
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry NOTCH Signaling as a Novel Cancer Therapeutic Target
Current Cancer Drug Targets Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship
Current Medicinal Chemistry The Synergistic Effect of Humanized Monoclonal Antibodies Targeting Insulin-Like Growth Factor 1 Receptor (IGF-1R) and Chemotherapy
Current Drug Targets Glycolipid Antigen – Mediated Invariant NKT Cell Activation in Microbial Immunity
Current Immunology Reviews (Discontinued) The Role of ING Tumor Suppressors in UV Stress Response and Melanoma Progression
Current Drug Targets Milk Thistle: A Future Potential Anti-Osteoporotic and Fracture Healing Agent
Current Drug Targets Psychoimmunological Analysis of Cancer Patients: Correlation with the Prognosis
Current Aging Science Bacterial Toxins: Potential Weapons Against HIV Infection
Current Pharmaceutical Design Therapeutic Applications of Crocus sativus L. (Saffron): A Review
The Natural Products Journal Alphavirus Vectors for Gene Therapy Applications
Current Gene Therapy Herbal Medicine of the 21st Century: A Focus on the Chemistry, Pharmacokinetics and Toxicity of Five Widely Advocated Phytotherapies
Current Topics in Medicinal Chemistry Current Management of Neonatal Neuroblastoma
Current Pediatric Reviews The Role of Mammalian Target of Rapamycin (mTOR) Inhibitors in the Treatment of Solid Tumors
Current Cancer Therapy Reviews Herpes Simplex Virus Vectors for Gene Delivery to a Variety of Different Cell Types
Current Gene Therapy Epidermal Growth Factor Receptor Irreversible Inhibitors: Chemical Exploration of the Cysteine-Trap Portion
Mini-Reviews in Medicinal Chemistry The Role of Phenolic Compounds in the Fight against Cancer – A Review
Anti-Cancer Agents in Medicinal Chemistry Antiproliferative and Antifungal Activities of 1,3-diarylpropane-1,3-diones Commonly used as Sunscreen Agents
Letters in Drug Design & Discovery miRNAs Highlights in Stem and Cancer Cells
Mini-Reviews in Medicinal Chemistry DNA Methyltransferases Inhibitors from Natural Sources
Current Topics in Medicinal Chemistry