Abstract
The bicyclam AMD3100 (originally called JM3100), in which the two cyclam rings are tethered by an aromatic bridge, emanated from JM2763, where the two cyclam moieties are tethered by an aliphatic linker - JM2763 in turn originated from JM1657, where the cyclam rings are directly linked to one another via a C-C bridge, and which was identified as an impurity, showing anti-HIV activity, in a commercial cyclam preparation. AMD3100 proved very effective against HIV-1 and HIV-2, inhibiting virus replication within the nM range, without toxicity for the host cells at concentrations that were > 100,000-fold higher than those required to inhibit HIV replication. The anti-HIV activity of AMD3100 appeared to be confined to the Tlymphotropic (X4) HIV strains, i.e. those strains that use the CXCR4 receptor to enter their target cells, and AMD3100 as of today still stands as one of the most potent and selective CXCR4 antagonists ever discovered. Hence, AMD3100 was found to interfere with a number of (patho)physiological processes which depend on the interaction of CXCR4 with its natural ligand, stromal derived factor (SDF-1) and which play an important role in rheumatoid, allergic and malignant diseases. AMD3100 has been shown to mobilize CD34+ stem cells from the bone marrow into the bloodstream and has also been shown to augment migration of bone marrowderived endothelial progenitor cells into sites of neovascularization after myocardial infarction. Currently, AMD3100 is actively pursued as a stem cell mobilizer for transplantation in patients with multiple myeloma and non-Hodgkins lymphoma.
Keywords: human immunodeficiency virus (hiv), reverse transcriptase (rt), cyclam, anti-hiv activity, glycoprotein gp120, cxcr4 antagonists, fusion inhibitor
Mini-Reviews in Medicinal Chemistry
Title: Potential Clinical Applications of the CXCR4 Antagonist Bicyclam AMD3100
Volume: 5 Issue: 9
Author(s): Erik De Clercq
Affiliation:
Keywords: human immunodeficiency virus (hiv), reverse transcriptase (rt), cyclam, anti-hiv activity, glycoprotein gp120, cxcr4 antagonists, fusion inhibitor
Abstract: The bicyclam AMD3100 (originally called JM3100), in which the two cyclam rings are tethered by an aromatic bridge, emanated from JM2763, where the two cyclam moieties are tethered by an aliphatic linker - JM2763 in turn originated from JM1657, where the cyclam rings are directly linked to one another via a C-C bridge, and which was identified as an impurity, showing anti-HIV activity, in a commercial cyclam preparation. AMD3100 proved very effective against HIV-1 and HIV-2, inhibiting virus replication within the nM range, without toxicity for the host cells at concentrations that were > 100,000-fold higher than those required to inhibit HIV replication. The anti-HIV activity of AMD3100 appeared to be confined to the Tlymphotropic (X4) HIV strains, i.e. those strains that use the CXCR4 receptor to enter their target cells, and AMD3100 as of today still stands as one of the most potent and selective CXCR4 antagonists ever discovered. Hence, AMD3100 was found to interfere with a number of (patho)physiological processes which depend on the interaction of CXCR4 with its natural ligand, stromal derived factor (SDF-1) and which play an important role in rheumatoid, allergic and malignant diseases. AMD3100 has been shown to mobilize CD34+ stem cells from the bone marrow into the bloodstream and has also been shown to augment migration of bone marrowderived endothelial progenitor cells into sites of neovascularization after myocardial infarction. Currently, AMD3100 is actively pursued as a stem cell mobilizer for transplantation in patients with multiple myeloma and non-Hodgkins lymphoma.
Export Options
About this article
Cite this article as:
De Clercq Erik, Potential Clinical Applications of the CXCR4 Antagonist Bicyclam AMD3100, Mini-Reviews in Medicinal Chemistry 2005; 5 (9) . https://dx.doi.org/10.2174/1389557054867075
DOI https://dx.doi.org/10.2174/1389557054867075 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Drugs and mitochondria
Mitochondria play a central role in the life and death of cells. They are not merely the center for energy metabolism but are also the headquarters for different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Mitochondria maintain homeostasis in the cell by interacting with reactive oxygen-nitrogen species ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer’s, Parkinson’s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment
Current Neuropharmacology Recent Developments of Coumarin Hybrids as Anti-fungal Agents
Current Topics in Medicinal Chemistry Cardiovascular Complications of HIV Infection and Treatment
Cardiovascular & Hematological Agents in Medicinal Chemistry β-Adrenergic Over-Stimulation and Cardio-Myocyte Apoptosis: Two Receptors, One Organelle, Two Fates?
Current Drug Targets Recombinant Interleukin-12 for Immunotherapy: A Double-Sided Sword
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Choline Kinase: An Important Target for Cancer
Current Medicinal Chemistry Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs
Pharmaceutical Nanotechnology Heptahelical Receptors for Lysolipids in Lymphocytes as Targets for Therapeutic Intervention
Drug Design Reviews - Online (Discontinued) Combating P-glycoprotein-Mediated Multidrug Resistance Using Therapeutic Nanoparticles
Current Pharmaceutical Design Effect of Curcumin on Pro-angiogenic Factors in the Xenograft Model of Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Physicochemical Characteristics Of Novel P-Glycoprotein Inhibitors Of The Cage Dimeric 1,4-Dihydropyridine Type
Medicinal Chemistry Next Generation Sequencing in the Management of Leptomeningeal Metastases of Non-Small Cell Lung Cancer: A Case Report and Literature Review
Recent Patents on Anti-Cancer Drug Discovery Alkylboronate Synthesis Based on Transition Metal-Catalyzed Hydroboration.
Current Organic Synthesis Exploring the Efficacy of Herbal Medications in the Treatment of Parkinsonism: A Mini Review
Current Drug Therapy Modelling and Measuring Redox Cycling and Cytotoxicity of Quinones
Drug Metabolism Letters Kinase Inhibitors in Multitargeted Cancer Therapy
Current Medicinal Chemistry Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part I: Xanthones, Quinones, Steroids, Coumarins, Phenolics and other Classes of Compounds
Anti-Cancer Agents in Medicinal Chemistry Proteomics on Fixed Tissue Specimens – A Review
Current Proteomics Myokines in Myogenesis and Health
Recent Patents on Biotechnology