Abstract
Aim and Objective: Anaplastic lymphoma kinase, an insulin receptor protein-tyrosine kinase, is a very attractive receptor protein target for anticancer therapy. This study was undertaken to identify novel structurally diverse anaplastic lymphoma kinase inhibitors.
Material and Method: Pharmacophore hypotheses modeling, virtual screening and molecular docking were used to detect potential inhibitors of anaplastic lymphoma kinase in this paper.
Results: After the generation of ten pharmacophore hypotheses, Hypo1 with the highest correlation value (0.981), lowest RMS (0.565), highest cost difference (83.850) along with four typical chemical features was regarded as the best hypothesis. Hypo1 contains a hydrogen bond acceptor, a hydrogen bong donor, a hydrophobic and a ring aromatic feature. And then, hypo1 was validated and used to screen three databases after screened by Lipinski’s rule of five. 3015 hits screened by Hypo1 were submitted to molecular docking based on the crystal structure of anaplastic lymphoma kinase.
Conclusion: all the seven molecules formed hydrogen bond interaction with Met1199 as well as formed several other hydrogen bond interactions with different residues. All of them formed Van Der Waals interaction with hydrophobic pocket which made up of residues of Ala1148, Leu1256, Leu1196, Leu1198 Val1130 and Val1180. Some of them also formed van der Waals interaction in somewhere else of protein pocket.
Keywords: Anaplastic lymphoma kinase, discovery studio, pharmacophore, virtual screening, molecular docking.
Combinatorial Chemistry & High Throughput Screening
Title:Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular Docking
Volume: 19 Issue: 9
Author(s): Rong You, Lu Zhou, Liangliang Zhong, Xiaoli Li, Suwen Zhou and Yahui Tian
Affiliation:
Keywords: Anaplastic lymphoma kinase, discovery studio, pharmacophore, virtual screening, molecular docking.
Abstract: Aim and Objective: Anaplastic lymphoma kinase, an insulin receptor protein-tyrosine kinase, is a very attractive receptor protein target for anticancer therapy. This study was undertaken to identify novel structurally diverse anaplastic lymphoma kinase inhibitors.
Material and Method: Pharmacophore hypotheses modeling, virtual screening and molecular docking were used to detect potential inhibitors of anaplastic lymphoma kinase in this paper.
Results: After the generation of ten pharmacophore hypotheses, Hypo1 with the highest correlation value (0.981), lowest RMS (0.565), highest cost difference (83.850) along with four typical chemical features was regarded as the best hypothesis. Hypo1 contains a hydrogen bond acceptor, a hydrogen bong donor, a hydrophobic and a ring aromatic feature. And then, hypo1 was validated and used to screen three databases after screened by Lipinski’s rule of five. 3015 hits screened by Hypo1 were submitted to molecular docking based on the crystal structure of anaplastic lymphoma kinase.
Conclusion: all the seven molecules formed hydrogen bond interaction with Met1199 as well as formed several other hydrogen bond interactions with different residues. All of them formed Van Der Waals interaction with hydrophobic pocket which made up of residues of Ala1148, Leu1256, Leu1196, Leu1198 Val1130 and Val1180. Some of them also formed van der Waals interaction in somewhere else of protein pocket.
Export Options
About this article
Cite this article as:
You Rong, Zhou Lu, Zhong Liangliang, Li Xiaoli, Zhou Suwen and Tian Yahui, Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular Docking, Combinatorial Chemistry & High Throughput Screening 2016; 19 (9) . https://dx.doi.org/10.2174/1386207319666160801153455
DOI https://dx.doi.org/10.2174/1386207319666160801153455 |
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
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
Integrating Network Pharmacology and Traditional Medicine: A New Perspective in Drug Mechanism Research
Network pharmacology is a network construction and network topology analysis strategy that combines pharmacology and pharmacodynamics. In recent years, network pharmacology has emerged as a powerful tool that can be integrated with pharmacology. Natural products commonly function in multicomponent, multitarget, and multipathway systems. Some examples encompass Ayurveda, traditional Chinese medicines ...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
-
Developments Towards a Prophylactic Hepatitis C Virus Vaccine
Current Immunology Reviews (Discontinued) Dendritic Cell Immunotherapy for Melanoma
Reviews on Recent Clinical Trials Therapeutic Polycomb Targeting in Human Cancer
Recent Patents on Regenerative Medicine miRNAs as Modulators of Cholesterol in Breast Cancer Stem Cells: An Approach to Overcome Drug Resistance in Cancer
Current Drug Targets Gene Therapy of Cancer Based on Interleukin 12
Current Gene Therapy Recent Development of Anticancer Therapeutics Targeting Akt
Recent Patents on Anti-Cancer Drug Discovery Recent Trials for FTY720 (Fingolimod): A New Generation of Immunomodulators Structurally Similar to Sphingosine
Reviews on Recent Clinical Trials The Past, Present and Future Subclassification of Patients with Acute Myeloid Leukemia
Current Pharmaceutical Biotechnology Inhibition of DNA Polymerase λ Suppresses 12-O-Tetradecanoylphorbol- 13-Acetate-Induced Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Yttrium-90 – Current Status, Expected Availability and Applications of a High Beta Energy Emitter
Current Radiopharmaceuticals Editorial (Thematic Issue: Oncoviruses and Head and Neck Cancer: An Impending Facts)
Recent Patents on Biomarkers Molecular Modeling Based Synthesis and Evaluation of <i>In vitro</i> Anticancer Activity of Indolyl Chalcones
Current Topics in Medicinal Chemistry New Purine Nucleoside Analogs for Acute Lymphoblastic Leukemia
Clinical Cancer Drugs Ginsenoside RB1 Reduces Neurologic Damage, is Anti-Apoptotic, and Down-Regulates p53 and BAX in Subarachnoid Hemorrhage
Current Neurovascular Research Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise
Current Pharmaceutical Design E2F1-Mediated Apoptosis as a Target of Cancer Therapy
Current Molecular Pharmacology Laboratory Diagnosis and Therapy of Invasive Fungal Infections
Current Drug Targets Importance of Influx and Efflux Systems and Xenobiotic Metabolizing Enzymes in Intratumoral Disposition of Anticancer Agents
Current Cancer Drug Targets Evaluation of Echocardiographic Abnormalities in HIV Positive Patients Treated with Antiretroviral Medications
Infectious Disorders - Drug Targets ACP5: Its Structure, Distribution, Regulation and Novel Functions
Anti-Cancer Agents in Medicinal Chemistry