Abstract
MERTK plays an important role in cell biology and is correlated with many cancers, such as mantle cell lymphomas, pituitary adenomas, and T-cell acute lympholoblastic leukemia. So identification of new MERTK inhibitors is of extreme importance. In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR model, which had high value of coefficient of determination (R2=0.9061) and high value of coefficient of determination (Q2=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits were obtained. Subsequently, docking procedure was applied on these hits, and 840 compounds were obtained through high-throughput virtual screening (HTVS). Standard precision (SP), extra precision (XP) and rule of five were also used in virtual screening protocol. Finally, six candidates were identified as potential MERTK inhibitors, with the docking mode in MERTK analyzed.
Keywords: MERTK inhibitors, pharmacophore, 3D-QSAR, virtual screening, molecular docking, ADME.
Combinatorial Chemistry & High Throughput Screening
Title:Pharmacophore-Based 3D-QSAR Modeling, Virtual Screening and Molecular Docking Analysis for the Detection of MERTK Inhibitors with Novel Scaffold
Volume: 19 Issue: 1
Author(s): Suwen Zhou, Lu Zhou, Ruguo Cui, Yahui Tian, Xiaoli Li, Rong You and Liangliang Zhong
Affiliation:
Keywords: MERTK inhibitors, pharmacophore, 3D-QSAR, virtual screening, molecular docking, ADME.
Abstract: MERTK plays an important role in cell biology and is correlated with many cancers, such as mantle cell lymphomas, pituitary adenomas, and T-cell acute lympholoblastic leukemia. So identification of new MERTK inhibitors is of extreme importance. In this study, 107 MERTK inhibitors with known activities were gathered to generate a ligand-based pharmacophore model (ADDHH.4), followed by building a 3D-QSAR model, which had high value of coefficient of determination (R2=0.9061) and high value of coefficient of determination (Q2=0.7442). For the pharmacophore model, two hydrogen bond donors (D), one hydrogen bond receptor (A), and two hydrophobic groups (H) were considered as the key elements contributing to ligand activity. The model then served to search a drug-like database with 1.5 million molecules, and 47832 hits were obtained. Subsequently, docking procedure was applied on these hits, and 840 compounds were obtained through high-throughput virtual screening (HTVS). Standard precision (SP), extra precision (XP) and rule of five were also used in virtual screening protocol. Finally, six candidates were identified as potential MERTK inhibitors, with the docking mode in MERTK analyzed.
Export Options
About this article
Cite this article as:
Zhou Suwen, Zhou Lu, Cui Ruguo, Tian Yahui, Li Xiaoli, You Rong and Zhong Liangliang, Pharmacophore-Based 3D-QSAR Modeling, Virtual Screening and Molecular Docking Analysis for the Detection of MERTK Inhibitors with Novel Scaffold, Combinatorial Chemistry & High Throughput Screening 2016; 19 (1) . https://dx.doi.org/10.2174/1386207319666151203002228
DOI https://dx.doi.org/10.2174/1386207319666151203002228 |
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
-
Peptide Nucleic Acids: A Novel Approach
Current Chemical Biology The Neuroprotective Effect of Ginkgo biloba Leaf Extract and its Possible Mechanism
Central Nervous System Agents in Medicinal Chemistry Quantum Dots in the Therapy: Current Trends and Perspectives
Mini-Reviews in Medicinal Chemistry Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility
Anti-Cancer Agents in Medicinal Chemistry Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry Monoclonal Antibodies: A Prospective and Retrospective View
Current Medicinal Chemistry Evaluation of Brazilian Biotechnology Patent Activity from 1975 to 2010
Recent Patents on DNA & Gene Sequences Limiting Functional Deficiency Following Stroke: Exploiting Different Stem Cell Reservoirs
Current Neuropharmacology The Rb Pathway and Cancer Therapeutics
Current Drug Targets Potential of Resveratrol in Preventing the Development of Heart Failure
Current Chemical Biology Folate Nutrigenetics: A Convergence of Dietary Folate Metabolism, Folic Acid Supplementation, and Folate Antagonist Pharmacogenetics
Drug Metabolism Letters Chebulagic Acid Synergizes the Cytotoxicity of Doxorubicin in Human Hepatocellular Carcinoma Through COX-2 Dependant Modulation of MDR-1
Medicinal Chemistry Pin1: A New Outlook in Alzheimers Disease
Current Alzheimer Research MicroRNAs in Chronic Lymphocytic Leukemia: An Old Disease with New Genetic Insights
MicroRNA Targeted Therapy for Advanced Prostate Cancer: Inhibition of the PI3K/Akt/mTOR Pathway
Current Cancer Drug Targets Adrenomedullin as a Potential Therapeutic Agent for Inflammatory Bowel Disease
Current Protein & Peptide Science Premature Ageing Prevention: Limitations and Perspectives of Pharmacological Interventions
Current Drug Targets Metastatic Cancer Stem Cells: New Molecular Targets for Cancer Therapy
Current Pharmaceutical Biotechnology Clinical Applications of <sup>18</sup>F-FDG PET/CT in Monitoring Anti-cancer Therapies
Current Pharmaceutical Biotechnology Immunotoxicity and Immunogenicity of Biopharmaceuticals: Design Concepts and Safety Assessment
Current Drug Safety