Abstract
Lipopolysaccharide (LPS) or endotoxin, the major constituent of the outer membrane of Gram negative bacteria, has been implicated as the bacterial product responsible for the clinical syndrome of sepsis. LPS binding to the host receptor Toll-like receptor 4 (TLR4) triggers an inflammatory reaction characterised by the release of large number of inflammatory mediators that allow the host to respond to the invading pathogen. When this production becomes uncontrolled and excessive, it leads to the development of septic shock. Despite decades of efforts in supporting therapies , sepsis remains the leading cause of death amongst critically ill patients. Unfortunately, the major factor contributing to the high morbidity and mortality of sepsis is the lack of the effective targeted treatment. Indeed, over 30 drugs for the treatment of sepsis have been developed: many of these target specific inflammatory mediators and have thus been, in general, unsuccessful since sepsis relies on the cross talk of several cytokines and the block of a single factor has been proven to be ineffective. More successful strategies include those modulating the early phase of LPS signalling such as the ones that prevent the binding of LPS to host cells and the subsequent cascade of detrimental events. In this light, effective LPS antagonists would represent invaluable tools to efficaciously manage sepsis. This review discusses the evolution of naturally occurring and synthetic LPS antagonists with emphasis on the development of several natural new molecules.
Keywords: Innate immunity, lipid A, lipopolysaccharide, sepsis, Toll-like receptor 4
Mini-Reviews in Medicinal Chemistry
Title: New Insight in LPS Antagonist
Volume: 9 Issue: 3
Author(s): A. Ianaro, M. Tersigni and F. D'Acquisto
Affiliation:
Keywords: Innate immunity, lipid A, lipopolysaccharide, sepsis, Toll-like receptor 4
Abstract: Lipopolysaccharide (LPS) or endotoxin, the major constituent of the outer membrane of Gram negative bacteria, has been implicated as the bacterial product responsible for the clinical syndrome of sepsis. LPS binding to the host receptor Toll-like receptor 4 (TLR4) triggers an inflammatory reaction characterised by the release of large number of inflammatory mediators that allow the host to respond to the invading pathogen. When this production becomes uncontrolled and excessive, it leads to the development of septic shock. Despite decades of efforts in supporting therapies , sepsis remains the leading cause of death amongst critically ill patients. Unfortunately, the major factor contributing to the high morbidity and mortality of sepsis is the lack of the effective targeted treatment. Indeed, over 30 drugs for the treatment of sepsis have been developed: many of these target specific inflammatory mediators and have thus been, in general, unsuccessful since sepsis relies on the cross talk of several cytokines and the block of a single factor has been proven to be ineffective. More successful strategies include those modulating the early phase of LPS signalling such as the ones that prevent the binding of LPS to host cells and the subsequent cascade of detrimental events. In this light, effective LPS antagonists would represent invaluable tools to efficaciously manage sepsis. This review discusses the evolution of naturally occurring and synthetic LPS antagonists with emphasis on the development of several natural new molecules.
Export Options
About this article
Cite this article as:
Ianaro A., Tersigni M. and D'Acquisto F., New Insight in LPS Antagonist, Mini-Reviews in Medicinal Chemistry 2009; 9 (3) . https://dx.doi.org/10.2174/1389557510909030306
DOI https://dx.doi.org/10.2174/1389557510909030306 |
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
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...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
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
Related Articles
-
Transition Metal Based Anticancer Drugs
Current Topics in Medicinal Chemistry p53-Independent Activities of MDM2 and Their Relevance to Cancer Therapy
Current Cancer Drug Targets Evaluation of Vitamin C as a Personalized Adjuvant Medicine: Pharmacogenomic Studies
Current Pharmacogenomics and Personalized Medicine RNA Splicing Manipulation: Strategies to Modify Gene Expression for a Variety of Therapeutic Outcomes
Current Gene Therapy The Signaling Function of the IL-13Rα2 Receptor in the Development of Gastrointestinal Fibrosis and Cancer Surveillance
Current Molecular Medicine Imatinib Mesylate: Targeted Therapy of Gastrointestinal Stromal Tumor
Current Cancer Therapy Reviews Next Generation Sequencing in Non-Small Cell Lung Cancer: New Avenues Toward the Personalized Medicine
Current Drug Targets Combined Treatment with PPAR-γ Agonists in Pancreatic Cancer: A Glimmer of Hope for Cancer Therapy?
Current Cancer Drug Targets A Review of Recent Patents Concerning Therapy of Respiratory Diseases Using Gene Silencing by RNAi (RISC) and EGS (RNAse P)
Recent Patents on Inflammation & Allergy Drug Discovery Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets Tumor Necrosis Factor: Renaissance as a Cancer Therapeutic?
Current Cancer Drug Targets Ubiquitin-Protein Ligases - Novel Therapeutic Targets?
Current Protein & Peptide Science The Development of PDGF Receptor Inhibitors for the Treatment of Glioma: A Review
Letters in Drug Design & Discovery BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK
Anti-Cancer Agents in Medicinal Chemistry Gemcitabine: A Critical Nucleoside for Cancer Therapy
Current Medicinal Chemistry Nanocarriers to Solid Tumors: Considerations on Tumor Penetration and Exposure of Tumor Cells to Therapeutic Agents
Current Pharmaceutical Biotechnology Targeted Genome Editing Tools for Disease Modeling and Gene Therapy
Current Gene Therapy Pattern of Care for Skin Cancers - Canada and France
Current Cancer Therapy Reviews Myxofibrosarcoma: Clinical and Prognostic Value of MRI Features
Current Medical Imaging Recent Advances of Kinesin Motor Inhibitors and their Clinical Progress
Reviews on Recent Clinical Trials