Abstract
The potential role of Autotaxin (ATX) in physiological and pathological processes turned it in an attractive drug target for pharmacological therapeutic development. However, potent and selective non-lipid as well lipid inhibitors of ATX are currently not available as drugs. In this paper we tried to review all the known progress on ATX inhibition using two dimensional (2D)-Quantitative Structure Activity Relationship (QSAR) and three dimensional (3D) mapping techniques. Furthermore, we tried to compare and extract conclusions analyzing with 3D mapping techniques vastly diverse structures of non-lipid ATX inhibitors which have been reported in patents. McGowan’s Volume (MgVol) molar volume and Molar Refractivity (MR) of substituents seems to govern the ATX inhibition. 3D-mapping results point to the role of steric properties (Volume and Polar Surface Area-PSA). Steric factors are obviously important. The role of hydrophilicity was also highlighted. Electronic parameters are not found to be present.
Keywords: 2D-QSAR, 3D-mapping, autotoxin inhibitors, inflammation, lipid mediators, non lipid, PK descriptors.
Current Medicinal Chemistry
Title:Considering Autotaxin Inhibitors in Terms of 2D-QSAR and 3D-Mapping- Review and Evaluation
Volume: 22 Issue: 12
Author(s): Sotirios Katsamakas, Eleftherios Bermperoglou and Dimitra Hadjipavlou-Litina
Affiliation:
Keywords: 2D-QSAR, 3D-mapping, autotoxin inhibitors, inflammation, lipid mediators, non lipid, PK descriptors.
Abstract: The potential role of Autotaxin (ATX) in physiological and pathological processes turned it in an attractive drug target for pharmacological therapeutic development. However, potent and selective non-lipid as well lipid inhibitors of ATX are currently not available as drugs. In this paper we tried to review all the known progress on ATX inhibition using two dimensional (2D)-Quantitative Structure Activity Relationship (QSAR) and three dimensional (3D) mapping techniques. Furthermore, we tried to compare and extract conclusions analyzing with 3D mapping techniques vastly diverse structures of non-lipid ATX inhibitors which have been reported in patents. McGowan’s Volume (MgVol) molar volume and Molar Refractivity (MR) of substituents seems to govern the ATX inhibition. 3D-mapping results point to the role of steric properties (Volume and Polar Surface Area-PSA). Steric factors are obviously important. The role of hydrophilicity was also highlighted. Electronic parameters are not found to be present.
Export Options
About this article
Cite this article as:
Katsamakas Sotirios, Bermperoglou Eleftherios and Hadjipavlou-Litina Dimitra, Considering Autotaxin Inhibitors in Terms of 2D-QSAR and 3D-Mapping- Review and Evaluation, Current Medicinal Chemistry 2015; 22 (12) . https://dx.doi.org/10.2174/0929867322666150227154253
DOI https://dx.doi.org/10.2174/0929867322666150227154253 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Transition Metal Based Anticancer Drugs
Current Topics in Medicinal Chemistry Role of microRNAs in Chronic Lymphocytic Leukemia Pathogenesis
Current Medicinal Chemistry Tankyrases: Structure, Function and Therapeutic Implications in Cancer
Current Pharmaceutical Design Discovery of Hedgehog Antagonists for Cancer Therapy
Current Medicinal Chemistry Future Prospect of RNA Interference for Cancer Therapies
Current Drug Targets Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery Regulation of Innate Immune Responses in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Mesenchymal Cells in the Treatment of Spinal Cord Injury: Current & Future Perspectives
Current Stem Cell Research & Therapy Advancing Drug Therapy for Brain Tumours: A Current Review of the Pro-inflammatory Peptide Substance P and its Antagonists as Anti-cancer Agents
Recent Patents on CNS Drug Discovery (Discontinued) Plants vs. Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability
Anti-Cancer Agents in Medicinal Chemistry Antibody Fragments as Potential Biopharmaceuticals for Cancer Therapy: Success and Limitations
Current Medicinal Chemistry Insights into the Role of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Health and Disease
Current Chemical Biology Peptide Prodrugs for the Treatment of CNS Disorders: A Perspective for New Drugs
Current Medicinal Chemistry Elevated Levels of Bilirubin and Long-Term Exposure Impair Human Brain Microvascular Endothelial Cell Integrity
Current Neurovascular Research Nongenomic Actions of Thyroid Hormones: From Basic Research to Clinical Applications. An Update
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Phytoconstituents of <i>Lantana camara</i> L.: Rekindling Hope in the Cancer Treatment
Current Bioactive Compounds The Potential Role of Pharmacogenomic and Genomic in the Adjuvant Treatment of Early Stage Non Small Cell Lung Cancer
Current Genomics Biomedical Technologies for In Vitro Screening and Controlled Delivery of Neuroactive Compounds
Central Nervous System Agents in Medicinal Chemistry Natural Products and Cancer Stem Cells
Current Pharmaceutical Design Subject Index To Volume-3
Letters in Drug Design & Discovery