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
-
Clinical Profile of Relaxin, a Possible New Drug for Human Use
Current Drug Safety Using an Ancient Tool for Igniting and Propagating Immune Tolerance: IDO as an Inducer and Amplifier of Regulatory T Cell Functions
Current Medicinal Chemistry The Potent Inhibitory Effect of β-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunosuppressive Property on Anti-Cyclic Citrullinated Peptide Antibodies, Rheumatoid Factor and Anti-dsDNA Antibodies in Patients with Rheumatoid Arthritis
Current Drug Discovery Technologies Formulation and Evaluation of Liposomal Drug Delivery System for Sulfasalazine
Current Nanomedicine Decreased Serum/Plasma Vitamin D levels in SLE Patients: A Meta-Analysis
Current Pharmaceutical Design Dual Cyclooxygenase and Carbonic Anhydrase Inhibition by Nonsteroidal Anti-Inflammatory Drugs for the Treatment of Cancer
Current Medicinal Chemistry Advances in Clinical Study of Curcumin
Current Pharmaceutical Design Modifier Gene Studies to Identify New Therapeutic Targets in Cystic Fibrosis
Current Pharmaceutical Design Novel Adjunctive Therapies for the Treatment of Tuberculosis
Current Molecular Medicine Moderate Hyperhomocysteinemia and Immune Activation
Current Pharmaceutical Biotechnology Synthesis and Biological Activity of a New Class of Azetidinones Compounds as Potential HLE Inhibitors
Letters in Drug Design & Discovery No Association of MicroRNA-146a rs2910164 Polymorphism and Risk of Primary Gout Development in Chinese Han Populations: A Case-control Study
Current Rheumatology Reviews MIF and CD74 - Suitability as Clinical Biomarkers
Mini-Reviews in Medicinal Chemistry Pharmacokinetics/Pharmacodynamics Model-Supported Early Drug Development
Current Pharmaceutical Biotechnology Interleukin-6 In Rheumatoid Arthritis - From The Laboratory To The Bedside
Current Pharmaceutical Design Therapeutic Targets in Inflammatory Disease
Current Medicinal Chemistry Cell Responses to Oxidative Stressors
Current Pharmaceutical Design Natural Compounds A Weapon to Ameliorate Breast Cancer Cells: A Review
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Neovascularization by the Implantation of Autologous Mononuclear Cells in Patients with Connective Tissue Diseases
Current Pharmaceutical Design Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging
Current Aging Science