Abstract
Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immune system homeostasis. TNF plays a critical role in host defense against infection, as well as an inhibitory role in autoimmune disease. However, TNF overproduction generates deleterious effects by inducing the transcription of genes involved in acute and chronic inflammatory responses including asthma, rheumatoid arthritis, Crohn´s disease, and psoriasis. Direct inhibition of TNF by biologics, such as monoclonal antibodies and circulating TNF receptor constructs, has produced effective treatments for these disorders and validated the inhibition of this proinflammatory cytokine as an effective therapy. Unfortunately, these biological therapies suffer from several drawbacks, including high cost and the induction of autoantibody production. Thus, the development of small molecules able to modulate TNF production or signaling pathways remains a central challenge in Medicinal Chemistry. Considerable efforts have been made over the past two decades to develop such inhibitors, which could potentially be administered orally and would presumably be cheaper. This review is focused on the recent development of compounds that modulate the activity of this cytokine by acting at different levels, such as TNF expression, processing, binding to its receptors and direct inhibition. These approaches will be compared and discussed.
Keywords: Cytokines, inflammation, protein-protein interactions, TNF, TNF inhibitors, TNF-TNFR interaction.
Current Medicinal Chemistry
Title:Small Molecules as Anti-TNF Drugs
Volume: 22 Issue: 25
Author(s): Victoria Richmond, Flavia M. Michelini, Carlos A. Bueno, Laura E. Alche and Javier A. Ramirez
Affiliation:
Keywords: Cytokines, inflammation, protein-protein interactions, TNF, TNF inhibitors, TNF-TNFR interaction.
Abstract: Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immune system homeostasis. TNF plays a critical role in host defense against infection, as well as an inhibitory role in autoimmune disease. However, TNF overproduction generates deleterious effects by inducing the transcription of genes involved in acute and chronic inflammatory responses including asthma, rheumatoid arthritis, Crohn´s disease, and psoriasis. Direct inhibition of TNF by biologics, such as monoclonal antibodies and circulating TNF receptor constructs, has produced effective treatments for these disorders and validated the inhibition of this proinflammatory cytokine as an effective therapy. Unfortunately, these biological therapies suffer from several drawbacks, including high cost and the induction of autoantibody production. Thus, the development of small molecules able to modulate TNF production or signaling pathways remains a central challenge in Medicinal Chemistry. Considerable efforts have been made over the past two decades to develop such inhibitors, which could potentially be administered orally and would presumably be cheaper. This review is focused on the recent development of compounds that modulate the activity of this cytokine by acting at different levels, such as TNF expression, processing, binding to its receptors and direct inhibition. These approaches will be compared and discussed.
Export Options
About this article
Cite this article as:
Richmond Victoria, Michelini M. Flavia, Bueno A. Carlos, Alche E. Laura and Ramirez A. Javier, Small Molecules as Anti-TNF Drugs, Current Medicinal Chemistry 2015; 22 (25) . https://dx.doi.org/10.2174/0929867322666150729115553
DOI https://dx.doi.org/10.2174/0929867322666150729115553 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Nitrergic Modulation of Gastrointestinal Function During Early Endotoxemia
Current Pharmaceutical Design <i>Scaphechinus mirabilis</i> Extract Effectively Inhibits the Proliferation of BPH-1 and LNCaP Prostate Epithelial Cells
The Natural Products Journal Beta-Blockers and Nitrates: Pharmacotherapy and Indications
Cardiovascular & Hematological Agents in Medicinal Chemistry Natural Products: A Rich Source of Antiviral Drug Lead Candidates for the Management of COVID-19
Current Pharmaceutical Design The Use of Infliximab in Dermatology
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events
Current Medicinal Chemistry Purine Ionotropic (P2X) Receptors
Current Pharmaceutical Design Beta-Blocking Agents and Electroconvulsive Therapy
Current Drug Therapy A Review on Phytochemistry and Pharmacology of Medicinal as well as Poisonous Mushrooms
Mini-Reviews in Medicinal Chemistry Cardiovascular Effects of Modulators of Soluble Guanylyl Cyclase Activity
Cardiovascular & Hematological Agents in Medicinal Chemistry An Exceptional Case of Atrial Fibrillation Arrhythmia Induced by Etoposide
Current Drug Safety Restoring the Dysfunctional Endothelium
Current Pharmaceutical Design Anticancer Potential of Thiazole Derivatives: A Retrospective Review
Mini-Reviews in Medicinal Chemistry Drug Reinforcement in a Rat Model of Attention Deficit/Hyperactivity Disorder – The Spontaneously Hypertensive Rat (SHR)
Current Drug Abuse Reviews Geriatric Depression - Review for Primary Care
Current Psychiatry Reviews Molecular Pathways of Endothelial Cell Activation for (Targeted) Pharmacological Intervention of Chronic Inflammatory Diseases
Current Vascular Pharmacology Glucose Control and Use of Continuous Glucose Monitoring in the Intensive Care Unit: A Critical Review
Current Diabetes Reviews Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Sepsis (Guest Editor: David E. Joyce)]
Current Drug Targets Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery
Current Pharmaceutical Design