Abstract
The seven-spanning transmembrane G-protein coupled receptor CXCR4, which specifically binds to the chemokine CXCL12, is expressed on many cell types, including various types of tumour cells. CXCR4 plays a crucial role in organ-specific metastasis, directing migration of malignant cells expressing this receptor toward microenvironments where the cognate ligand is secreted. CXCL12 has a direct growth and survival-promoting effect for various cancer cells and enhances moreover tumour angiogenesis by recruiting endothelial progenitor cells to tumours. Drugs which modulate the CXCL12/CXCR4 axis are therefore promising candidates in anti-cancer therapies. CXCR4 is also a coreceptor for human immunodeficiency virus type 1 (HIV-1) X4 virus and, as such, plays an important role in virus entry into target cells. Hence, antiviral agents that bind to CXCR4 are expected to inhibit HIV-1 entry. Here we review the structure, mechanism of action and biological activity of the main CXCR4 antagonists (peptide inhibitors, non-peptide antagonists, neutralizing antibodies, modified analogues of CXCL12) and agonists (CXCL12 peptide analogues) and discuss the CXCL12/CXCR4 axis as an important target in development of anti-tumoral and anti-HIV-1 therapies.
Keywords: CXCR4, CXCL12, antagonist, agonist, analogue, cancer, HIV-1, hematopoietic progenitor mobilization, cognate ligand, angiogenesis, human immunodeficiency virus type 1, peptide inhibitors,, chemokine receptors, G-protein coupled receptor (GPCR), bone marrow, lymph nodes, lung, brain, liver, peptide, Tachypleus tridentatus, Limulus polyphemus, TZ14004, TN14003, TC14012, 4F-benzoyl-TN14003, T-140-Based Cyclic Pentapeptides, Linear T140-Based Oligopeptides, tripeptide mimetics, p-fluorobenzoylated tripeptide mimetics, AMD3100, AMD3100-Based Non-Cyclam Compounds, Dipicolylamine zinc(II)-Based Compounds, HSEFFR-CPC-RFFESH, aberrant hematopoiesi, homodimerization, Epstein-Barr virus-encoded
Current Medicinal Chemistry
Title: The CXCL12/CXCR4 Axis as a Therapeutic Target in Cancer and HIV-1 Infection
Volume: 18 Issue: 4
Author(s): L. Patrussi and C. T. Baldari
Affiliation:
Keywords: CXCR4, CXCL12, antagonist, agonist, analogue, cancer, HIV-1, hematopoietic progenitor mobilization, cognate ligand, angiogenesis, human immunodeficiency virus type 1, peptide inhibitors,, chemokine receptors, G-protein coupled receptor (GPCR), bone marrow, lymph nodes, lung, brain, liver, peptide, Tachypleus tridentatus, Limulus polyphemus, TZ14004, TN14003, TC14012, 4F-benzoyl-TN14003, T-140-Based Cyclic Pentapeptides, Linear T140-Based Oligopeptides, tripeptide mimetics, p-fluorobenzoylated tripeptide mimetics, AMD3100, AMD3100-Based Non-Cyclam Compounds, Dipicolylamine zinc(II)-Based Compounds, HSEFFR-CPC-RFFESH, aberrant hematopoiesi, homodimerization, Epstein-Barr virus-encoded
Abstract: The seven-spanning transmembrane G-protein coupled receptor CXCR4, which specifically binds to the chemokine CXCL12, is expressed on many cell types, including various types of tumour cells. CXCR4 plays a crucial role in organ-specific metastasis, directing migration of malignant cells expressing this receptor toward microenvironments where the cognate ligand is secreted. CXCL12 has a direct growth and survival-promoting effect for various cancer cells and enhances moreover tumour angiogenesis by recruiting endothelial progenitor cells to tumours. Drugs which modulate the CXCL12/CXCR4 axis are therefore promising candidates in anti-cancer therapies. CXCR4 is also a coreceptor for human immunodeficiency virus type 1 (HIV-1) X4 virus and, as such, plays an important role in virus entry into target cells. Hence, antiviral agents that bind to CXCR4 are expected to inhibit HIV-1 entry. Here we review the structure, mechanism of action and biological activity of the main CXCR4 antagonists (peptide inhibitors, non-peptide antagonists, neutralizing antibodies, modified analogues of CXCL12) and agonists (CXCL12 peptide analogues) and discuss the CXCL12/CXCR4 axis as an important target in development of anti-tumoral and anti-HIV-1 therapies.
Export Options
About this article
Cite this article as:
Patrussi L. and T. Baldari C., The CXCL12/CXCR4 Axis as a Therapeutic Target in Cancer and HIV-1 Infection, Current Medicinal Chemistry 2011; 18 (4) . https://dx.doi.org/10.2174/092986711794480159
DOI https://dx.doi.org/10.2174/092986711794480159 |
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
-
Quantitative Proteomics for Cancer Biomarker Discovery
Combinatorial Chemistry & High Throughput Screening Molecular Pharmacology of Malignant Pleural Mesothelioma: Challenges and Perspectives From Preclinical and Clinical Studies
Current Drug Targets Bone Disease - Current Knowledge and Future Prospects
Current Genomics Flavonoids, Breast Cancer Chemopreventive and/or Chemotherapeutic Agents
Current Medicinal Chemistry The Influence of Salinomycin on the Expression Profile of mRNAs Encoding Selected Caspases and MiRNAs Regulating their Expression in Endometrial Cancer Cell Line
Current Pharmaceutical Biotechnology Pharmacologic Activation of p53 by Small-Molecule MDM2 Antagonists
Current Pharmaceutical Design Toxicity of Carbon Nanotubes
Current Drug Metabolism Longitudinal Melatonin Production in Female Laboratory Rats During 1997-2006: Possible Modulatory Effects of Changing Solar Activity
Current Aging Science Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules
Current Medicinal Chemistry Assessment of Medical Students’ Knowledge of Lynch Syndrome Cancers, Screening, and Prevention
Current Women`s Health Reviews Temporal Expression of miRNAs in Laser Capture Microdissected Palate Medial Edge Epithelium from Tgfβ3<sup>-/-</sup> Mouse Fetuses
MicroRNA Using Pharmacologic Data to Plan Clinical Treatments for Patients with Peritoneal Surface Malignancy
Current Drug Discovery Technologies Tamoxifen: Is it Safe? Comparison of Activation and Detoxication Mechanisms in Rodents and in Humans
Current Drug Metabolism Role of Androgens in Womens Sexual Function & Dysfunction: What Have We Learned in Six Decades?
Current Women`s Health Reviews Meta-analysis Reveals No Association of DNMT3B -149 C>T Gene Polymorphism With Overall Cancer Risk
Current Genomics High-density Lipoprotein, Vascular Risk, Cancer and Infection: A Case of Quantity and Quality?
Current Medicinal Chemistry Editorial (Thematic Issue: Epigenetic Regulation and Human Diseases)
Current Pharmaceutical Design Texture Analysis in the Evaluation of COVID-19 Pneumonia in Chest X-Ray Images: A Proof of Concept Study
Current Medical Imaging Amphiphilic Polysaccharide-Hydrophobicized Graft Polymeric Micelles for Drug Delivery Nanosystems
Current Medicinal Chemistry Development and Validation of a Five-immune Gene Pair Signature in Endometrial Carcinoma
Combinatorial Chemistry & High Throughput Screening