Abstract
Aim and objective: Rheumatoid Arthritis (RA) is a progressing autoimmune inflammatory disease of joint, hallmarked by inflammation, pain and atrophy of bones. Toll-like receptor 5 (TLR5) is a novel inflammatory mediator in RA, and TLR5 inhibitors are speculated to have a therapeutic potential for the treatment of RA.
Material and method: Here we applied fragment pharmacophore-based virtual screening to identify novel TLR5 ligands. Results: Among compounds collected from Otava peptidomimetic compounds, Maybridge fragment and ZINC libraries, 3355 compounds were selected for docking into the flagellin-binding site of TLR5. 16 compounds with the required interaction, critical amino acid residues and the binding free energies <-7 kcal/mol were identified as potential TLR5 inhibitors, one of which was followed up by molecular dynamics simulation. Conclusion: These compounds open a possibility to discover novel TLR5 inhibitors for the treatment of RA.Keywords: Fragment-based, molecular docking, pharmacophore model, TLR5, virtual screening, molecular dynamics.
Combinatorial Chemistry & High Throughput Screening
Title:Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5
Volume: 19 Issue: 10
Author(s): Hoora Hashemi, Malihe Hassanzadeh and Massoud Amanlou
Affiliation:
Keywords: Fragment-based, molecular docking, pharmacophore model, TLR5, virtual screening, molecular dynamics.
Abstract: Aim and objective: Rheumatoid Arthritis (RA) is a progressing autoimmune inflammatory disease of joint, hallmarked by inflammation, pain and atrophy of bones. Toll-like receptor 5 (TLR5) is a novel inflammatory mediator in RA, and TLR5 inhibitors are speculated to have a therapeutic potential for the treatment of RA.
Material and method: Here we applied fragment pharmacophore-based virtual screening to identify novel TLR5 ligands. Results: Among compounds collected from Otava peptidomimetic compounds, Maybridge fragment and ZINC libraries, 3355 compounds were selected for docking into the flagellin-binding site of TLR5. 16 compounds with the required interaction, critical amino acid residues and the binding free energies <-7 kcal/mol were identified as potential TLR5 inhibitors, one of which was followed up by molecular dynamics simulation. Conclusion: These compounds open a possibility to discover novel TLR5 inhibitors for the treatment of RA.Export Options
About this article
Cite this article as:
Hashemi Hoora, Hassanzadeh Malihe and Amanlou Massoud, Fragment Pharmacophore-Based Screening: An Efficient Approach for Discovery of New Inhibitors of Toll-Like Receptor 5, Combinatorial Chemistry & High Throughput Screening 2016; 19 (10) . https://dx.doi.org/10.2174/1386207319666160907103507
DOI https://dx.doi.org/10.2174/1386207319666160907103507 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to 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
-
Anti-Infective Strategies of the Future: Is there Room for Species-Specific Antibacterial Agents?
Current Pharmaceutical Design Host Genetic Factors and Treatment of Hepatitis C
Current Molecular Pharmacology Airway Clearance of Apoptotic Cells in COPD
Current Drug Targets Current Status of Complementary and Alternative Medicine in the Treatment of Rheumatic Disease Pain
Current Rheumatology Reviews The Immunoproteasome as a Therapeutic Target for Hematological Malignancies
Current Cancer Drug Targets A Medicinal Mushroom: Phellinus Linteus
Current Medicinal Chemistry Lipid based Nanocapsules: A Multitude of Biomedical Applications
Current Pharmaceutical Biotechnology CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery
Current Drug Targets New Strategies and Patent Therapeutics in EBV-Associated Diseases
Mini-Reviews in Medicinal Chemistry Immunotherapy with Tumor Vaccines for the Treatment of Malignant Gliomas
Current Drug Discovery Technologies Study on the Slow-Release Mometasone Furoate Injection of PLGA for the Treatment of Knee Arthritis
Current Drug Delivery Plant Natural Products in Anticancer Drug Discovery
Current Organic Chemistry Role of Chitosan Biomaterials in Drug Delivery Systems: A Patent Perspective
Recent Patents on Materials Science The Need for Diagnostic Criteria in Systemic Vasculitis
Current Immunology Reviews (Discontinued) MMP-2 Selectivity in Hydroxamate-Type Inhibitors
Current Medicinal Chemistry Vitamin D and the Adaptive Immune System with Special Emphasis to Allergic Reactions and Allograft Rejection
Inflammation & Allergy - Drug Targets (Discontinued) Role of Antioxidants, Essential Fatty Acids, Carnitine, Vitamins, Phytochemicals and Trace Elements in the Treatment of Diabetes Mellitus and its Chronic Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting BLyS in Systemic Lupus Erythematosus
Recent Patents on Inflammation & Allergy Drug Discovery HS-MMGKG: A Fast Multi-objective Harmony Search Algorithm for Two-locus Model Detection in GWAS
Current Bioinformatics Meet Our Editorial Board Member:
Current Nutrition & Food Science