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
-
Recent Advances in Immune Modulation
Current Gene Therapy Tubulin-Independent Tau in Alzheimer’s Disease and Cancer: Implications for Disease Pathogenesis and Treatment
Current Alzheimer Research Anti-Angiogenic and Anti-Inflammatory Effects of Statins: Relevance to Anti-Cancer Therapy
Current Cancer Drug Targets Novel Drug Therapies for Fertility Preservation in Men Undergoing Chemotherapy: Clinical Relevance of Protector Agents
Current Medicinal Chemistry Archaeosome Immunostimulatory Vaccine Delivery System
Current Drug Delivery Intraorganellar Acidification by V-ATPases: A Target in Cell Proliferation and Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Preclinical and Clinical Studies of Novel Breast Cancer Drugs Targeting Molecules Involved in Protein Kinase C Signaling, the Putative Metastasis-Suppressor Gene Cap43 and the Y-box Binding Protein-1
Current Medicinal Chemistry Respiratory Failure in Cancer Patients: Non-Infectious Complications of Antineoplastic Agents for Solid Tumors
Current Respiratory Medicine Reviews Modifications of Cell Signalling and Redox Balance by Targeting Protein Acetylation Using Natural and Engineered Molecules: Implications in Cancer Therapy
Current Topics in Medicinal Chemistry Current and Emerging Strategies in Bladder Cancer
Anti-Cancer Agents in Medicinal Chemistry Regulatory T Cells as Targets for Immunotherapy of Autoimmunity and Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Chemotherapeutic Targeting of Cell Death Pathways
Anti-Cancer Agents in Medicinal Chemistry Progenitor Cell Types in HIV-1 Infection: Bioactivity and Emerging Targets for Treatment
Current HIV Research Multidrug Resistance Through the Spectacle of P-Glycoprotein
Current Cancer Drug Targets Environmentally Sensitive Paramagnetic and Diamagnetic Contrast Agents for Nuclear Magnetic Resonance Imaging and Spectroscopy
Current Topics in Medicinal Chemistry Targeting of NF-kappaB Signaling Pathway, other Signaling Pathways and Epigenetics in Therapy of Multiple Myeloma
Cardiovascular & Hematological Disorders-Drug Targets Therapeutic Application of Histone Deacetylase Inhibitors for Stroke
Central Nervous System Agents in Medicinal Chemistry Cytochrome P450 Retinoic Acid 4-Hydroxylase Inhibitors: Potential Agents for Cancer Therapy
Mini-Reviews in Medicinal Chemistry Therapeutic Antibodies in HIV Treatment - Classical Approaches to Novel Advances
Current Pharmaceutical Design Anticoagulant and Fibrinolytic Drugs – Possible Agents in Treatment of Lung Cancer?
Anti-Cancer Agents in Medicinal Chemistry