Abstract
The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This system has recently been proven to be involved in several problematic diseases, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis (RA) and pulmonary fibrosis. Thus, CXCR4 is thought to be an important therapeutic target to overcome the above diseases. Fourteen-mer peptides, T140 and its analogs, were previously found to be specific CXCR4 antagonists that were characterized as HIV-entry inhibitors, anti-cancer-metastatic agents, anti-chronic lymphocytic/acute lymphoblastic leukemia agents and anti-RA agents. Based on our knowledge of pharmacophores of T140, CXCR4 antagonists, such as FC131, were previously found by the efficient utilization of cyclic pentapeptide libraries. This review article focuses on our recent research on the development of low molecular weight CXCR4 antagonists including FC131 analogs, in which structural tuning of the cyclic peptide ring and chemical modifications were performed for an increase in potency and a reduction of the peptide character.
Keywords: Leukemia cell progression, cancer metastasis, chemokine receptor, HIV infection, low molecular weight CXCR4 antagonist, rheumatoid arthritis, chemical biology, proteomics
Current Medicinal Chemistry
Title: Development of Low Molecular Weight CXCR4 Antagonists by Exploratory Structural Tuning of Cyclic Tetra- and Pentapeptide-Scaffolds Towards the Treatment of HIV Infection, Cancer Metastasis and Rheumatoid Arthritis
Volume: 14 Issue: 1
Author(s): Hirokazu Tamamura, Hiroshi Tsutsumi, Hiroyuki Masuno and Nobutaka Fujii
Affiliation:
Keywords: Leukemia cell progression, cancer metastasis, chemokine receptor, HIV infection, low molecular weight CXCR4 antagonist, rheumatoid arthritis, chemical biology, proteomics
Abstract: The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This system has recently been proven to be involved in several problematic diseases, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis (RA) and pulmonary fibrosis. Thus, CXCR4 is thought to be an important therapeutic target to overcome the above diseases. Fourteen-mer peptides, T140 and its analogs, were previously found to be specific CXCR4 antagonists that were characterized as HIV-entry inhibitors, anti-cancer-metastatic agents, anti-chronic lymphocytic/acute lymphoblastic leukemia agents and anti-RA agents. Based on our knowledge of pharmacophores of T140, CXCR4 antagonists, such as FC131, were previously found by the efficient utilization of cyclic pentapeptide libraries. This review article focuses on our recent research on the development of low molecular weight CXCR4 antagonists including FC131 analogs, in which structural tuning of the cyclic peptide ring and chemical modifications were performed for an increase in potency and a reduction of the peptide character.
Export Options
About this article
Cite this article as:
Tamamura Hirokazu, Tsutsumi Hiroshi, Masuno Hiroyuki and Fujii Nobutaka, Development of Low Molecular Weight CXCR4 Antagonists by Exploratory Structural Tuning of Cyclic Tetra- and Pentapeptide-Scaffolds Towards the Treatment of HIV Infection, Cancer Metastasis and Rheumatoid Arthritis, Current Medicinal Chemistry 2007; 14 (1) . https://dx.doi.org/10.2174/092986707779313499
DOI https://dx.doi.org/10.2174/092986707779313499 |
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
-
A Concept of Homeostatic Inflammation Provided by Endogenous TLR4 Agonists that Function Before and After Danger Signal for Metastasis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Stress as a Pathophysiological Factor in Functional Somatic Syndromes
Current Psychiatry Reviews Therapeutic Outlook of Pyrazole Analogs: A Mini Review
Mini-Reviews in Medicinal Chemistry Inhibitors of Nitrogen Oxide Species Production in Animal Models of Inflammation and Future Directions for Therapy in Inflammatory Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents ‘Osteoimmunology' Offers New Perspectives for the Treatment of Pathological Bone Loss
Current Pharmaceutical Design IRAK-4 Inhibitors for Inflammation
Current Topics in Medicinal Chemistry Integrin αvβ3 Antagonists for Anti-Angiogenic Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Thioredoxin Reductase and its Inhibitors
Current Protein & Peptide Science Chemokines in Rheumatic Diseases
Current Drug Targets CD20-based Immunotherapy of B-cell Derived Hematologic Malignancies
Current Cancer Drug Targets Adipokines as Novel Links between Obesity and Insulin Resistance
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Nutraceuticals in Psychiatric Practice
Recent Patents on CNS Drug Discovery (Discontinued) Development of Clinical Trial Assessments for the Study of Interstitial Lung Disease in Patients who have Connective Tissue Diseases-Methodological Considerations
Current Rheumatology Reviews Cyclosporin A: A Therapeutic Strategy in Allergic Diseases
Letters in Drug Design & Discovery Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry The Relevance of IgE in the Pathogenesis of Allergy: The Effect of an Anti-IgE Drug in Asthma and Other Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Targeting Cytokines for Morphine Tolerance: A Narrative Review
Current Neuropharmacology Plant Polyphenols and Oral Health: Old Phytochemicals for New Fields
Current Medicinal Chemistry Transitional Connective Tissue Diseases: Description of Four Cases
Current Rheumatology Reviews Pharmacokinetics/Pharmacodynamics Model-Supported Early Drug Development
Current Pharmaceutical Biotechnology