Abstract
The overexpression of Tumor Necrosis Factor (TNF) is directly related to the development of several autoimmune diseases, such as rheumatoid and psoriatic arthritis, inflammatory bowel disease, Crohn's disease, refractory asthma, and multiple sclerosis. Receptor Activator of Nuclear Factor Kappa- B Ligand (RANKL) belongs to the TNF family and is the primary mediator of osteoclast-induced bone resorption through interaction with its receptor RANK. The function of RANKL is physiologically inhibited by the action of osteoprotegerin (OPG), which is a decoy receptor that binds to RANKL and prevents the process of osteoclastogenesis. Malfunction among RANK/RANKL/OPG can also result in bone loss diseases, including postmenopausal osteoporosis, rheumatoid arthritis, bone metastasis and multiple myeloma. To disrupt the unwanted functions of TNF and RANKL, current attempts focus on blocking TNF and RANKL binding to their receptors. In this review, we present the research efforts toward the development of low-molecular-weight pharmaceuticals that directly block the detrimental actions of TNF and RANKL.
Keywords: Tumor Necrosis Factor (TNF), osteoprotegerin (OPG), postmenopausal osteoporosis, rheumatoid arthritis, disease, metastasis.
Graphical Abstract
Current Topics in Medicinal Chemistry
Title:Current Status and Future Prospects of Small–molecule Protein–protein Interaction (PPI) Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL)
Volume: 18 Issue: 8
Author(s): Georgia Melagraki, Georgios Leonis, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, George Kollias*Antreas Afantitis*
Affiliation:
- Division of Immunology, Biomedical Sciences Research Center `Alexander Fleming`, Vari,Greece
- Division of Immunology, Biomedical Sciences Research Center `Alexander Fleming`, Vari,Greece
Keywords: Tumor Necrosis Factor (TNF), osteoprotegerin (OPG), postmenopausal osteoporosis, rheumatoid arthritis, disease, metastasis.
Abstract: The overexpression of Tumor Necrosis Factor (TNF) is directly related to the development of several autoimmune diseases, such as rheumatoid and psoriatic arthritis, inflammatory bowel disease, Crohn's disease, refractory asthma, and multiple sclerosis. Receptor Activator of Nuclear Factor Kappa- B Ligand (RANKL) belongs to the TNF family and is the primary mediator of osteoclast-induced bone resorption through interaction with its receptor RANK. The function of RANKL is physiologically inhibited by the action of osteoprotegerin (OPG), which is a decoy receptor that binds to RANKL and prevents the process of osteoclastogenesis. Malfunction among RANK/RANKL/OPG can also result in bone loss diseases, including postmenopausal osteoporosis, rheumatoid arthritis, bone metastasis and multiple myeloma. To disrupt the unwanted functions of TNF and RANKL, current attempts focus on blocking TNF and RANKL binding to their receptors. In this review, we present the research efforts toward the development of low-molecular-weight pharmaceuticals that directly block the detrimental actions of TNF and RANKL.
Export Options
About this article
Cite this article as:
Melagraki Georgia , Leonis Georgios , Ntougkos Evangelos , Rinotas Vagelis , Papaneophytou Christos , Mavromoustakos Thomas , Kontopidis George , Douni Eleni , Kollias George *, Afantitis Antreas*, Current Status and Future Prospects of Small–molecule Protein–protein Interaction (PPI) Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL), Current Topics in Medicinal Chemistry 2018; 18 (8) . https://dx.doi.org/10.2174/1568026618666180607084430
DOI https://dx.doi.org/10.2174/1568026618666180607084430 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Carbon Monoxide-Releasing Molecules: A Pharmacological Expedient to Counteract Inflammation
Current Pharmaceutical Design Biosimilars for the Management of Inflammatory Bowel Diseases: Economic Considerations
Current Medicinal Chemistry Editorial [ Are Peptide Therapeutics the Future? Guest Editor: Sivaram Pillarisetti ]
Current Pharmaceutical Biotechnology An Update on Drug Interactions with the Herbal Medicine Ginkgo biloba
Current Drug Metabolism Mass Spectrometry Techniques: Principles and Practices for Quantitative Proteomics
Current Protein & Peptide Science Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery The Role of Oxidative Stress in Anti-tumor Necrosis Factor Antibody Treatment in Crohn´s Disease
Current Medicinal Chemistry Inhibition of Matrix Metalloproteinases as a Feasible Therapeutic Target in Rheumatoid Arthritis
Current Rheumatology Reviews Computer Aided Drug Design: Success and Limitations
Current Pharmaceutical Design Mannose Binding Lectin: A Potential Biomarker for Many Human Diseases
Current Medicinal Chemistry Treatment of Ankylosing Spondylitis with Biologic Agents
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Interferon-beta Inhibits Th17 Cell Differentiation in Patients with Multiple Sclerosis
Endocrine, Metabolic & Immune Disorders - Drug Targets Effects of Tea Catechins on Inflammation-Related Cardiovascular Diseases
Current Immunology Reviews (Discontinued) pH Modulation Based Solid Dispersion to Enhance Solubility of a Poorly Soluble NSAID - Development and Evaluation
Drug Delivery Letters Proteomic Analysis of Plasma to Reveal the Impact of Short-Term Etanercept Therapy in Pediatric Patients with Enthesitis-Related Arthritis: A Case Report
Combinatorial Chemistry & High Throughput Screening Modifiable Risk Factors for Premature Atherosclerosis in Systemic Lupus Erythematosus
Vascular Disease Prevention (Discontinued) Backbone-Cyclized Peptides: A Critical Review
Current Topics in Medicinal Chemistry Promiscuous Biological Features of Newly Emerged SARS-CoV-2 Facilitate its Unrestrained Outbreak: An Update
Coronaviruses The Detection of Anti-adalimumab Antibodies in a Series of Inflammatory Polyarthritis: three ELISA Methods Compared
Drug Metabolism Letters CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders
Current Drug Targets