Abstract
The cellular network and its environment govern cell and organism behavior and are fundamental to the comprehension of function, misfunction and drug discovery. Over the last few years, drugs were observed to often bind to more than one target; thus, polypharmacology approaches can be advantageous, complementing the “one drug - one target” strategy. Targeting drug discovery from the systems biology standpoint can help in studies of network effects of mono- and poly-pharmacology. In this mini-review, we provide an overview of the usefulness of network description and tools for mono- and poly-pharmacology, and the ways through which protein interactions can help single- and multi-target drug discovery efforts. We further describe how, when combined with experimental data, modeled structural networks which can predict which proteins interact and provide the structures of their interfaces, can model the cellular pathways, and suggest which specific pathways are likely to be affected. Such structural networks may facilitate structure-based drug design; forecast side effects of drugs; and suggest how the effects of drug binding can propagate in multi-molecular complexes and pathways.
Keywords: Poly-pharmacology, network pharmacology, protein-protein interaction inhibitors, systems biology, protein-protein interfaces, modeling.
Current Pharmaceutical Design
Title:Network-Based Strategies Can Help Mono- and Poly-pharmacology Drug Discovery: A Systems Biology View
Volume: 20 Issue: 8
Author(s): H. Billur Engin, Attila Gursoy, Ruth Nussinov and Ozlem Keskin
Affiliation:
Keywords: Poly-pharmacology, network pharmacology, protein-protein interaction inhibitors, systems biology, protein-protein interfaces, modeling.
Abstract: The cellular network and its environment govern cell and organism behavior and are fundamental to the comprehension of function, misfunction and drug discovery. Over the last few years, drugs were observed to often bind to more than one target; thus, polypharmacology approaches can be advantageous, complementing the “one drug - one target” strategy. Targeting drug discovery from the systems biology standpoint can help in studies of network effects of mono- and poly-pharmacology. In this mini-review, we provide an overview of the usefulness of network description and tools for mono- and poly-pharmacology, and the ways through which protein interactions can help single- and multi-target drug discovery efforts. We further describe how, when combined with experimental data, modeled structural networks which can predict which proteins interact and provide the structures of their interfaces, can model the cellular pathways, and suggest which specific pathways are likely to be affected. Such structural networks may facilitate structure-based drug design; forecast side effects of drugs; and suggest how the effects of drug binding can propagate in multi-molecular complexes and pathways.
Export Options
About this article
Cite this article as:
Engin Billur H., Gursoy Attila, Nussinov Ruth and Keskin Ozlem, Network-Based Strategies Can Help Mono- and Poly-pharmacology Drug Discovery: A Systems Biology View, Current Pharmaceutical Design 2014; 20 (8) . https://dx.doi.org/10.2174/13816128113199990066
DOI https://dx.doi.org/10.2174/13816128113199990066 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
The Role of AMPK/mTOR Modulators in the Therapy of Acute Myeloid Leukemia
Current Medicinal Chemistry Myeloma Cells and Their Interactions With the Bone Marrow Endothelial Cells
Current Immunology Reviews (Discontinued) Anticancer Alkylphospholipids: Mechanisms of Action, Cellular Sensitivity and Resistance, and Clinical Prospects
Current Pharmaceutical Design BCR/ABL1 Fusion Transcripts Generated from Alternative Splicing: Implications for Future Targeted Therapies in Ph+ Leukaemias
Current Molecular Medicine Molecular Link Mechanisms between Inflammation and Cancer
Current Pharmaceutical Design Emerging Role of Wnt/Beta-Catenin Signalling Pathways in Cancer Progression and Role of Small Molecule Tankyrase Inhibitors in Combating Multistage Cancers
Current Cancer Therapy Reviews Small Molecule Aurora Kinases Inhibitors
Current Medicinal Chemistry Epigenetic Multiple Modulators
Current Topics in Medicinal Chemistry Studies on Non-synonymous Polymorphisms Altering Human DNA Topoisomerase II-Alpha Interaction with Amsacrine and Mitoxantrone: An <i>In Silico</i> Approach
Current Cancer Drug Targets Editorial [Hot topic: The Urokinase Receptor System as Strategic Therapeutic Target: Challenges for the 21st Century (Executive Guest Editor: Bernard Degryse)]
Current Pharmaceutical Design Genomic Signatures for Individualized Treatment of Malignant Tumors
Current Drug Discovery Technologies Composite Lymphomas: A Challenging Entity
Current Cancer Therapy Reviews Flavopiridol, the First Cyclin-Dependent Kinase Inhibitor: Recent Advances in Combination Chemotherapy
Mini-Reviews in Medicinal Chemistry A Review of Recent Advancements in Anti-tubercular Molecular Hybrids
Current Medicinal Chemistry Cytotoxic and Apoptogenic Activity of a Methanolic Extract from the Marine Invertebrate Ciona intestinalis on Malignant Cell Lines
Medicinal Chemistry A Comprehensive Review on Perfusion Method Development for Bone Marrow Collection and Stem Cell Transplantation
Current Stem Cell Research & Therapy Innate Immunity and the Heart
Current Pharmaceutical Design Natural Products as a Source of Protein Kinase Activators and Inhibitors
Current Topics in Medicinal Chemistry Understanding Unmet Needs in the Older Acute Myeloid Leukemia (AML) Patient
Current Cancer Therapy Reviews Selection of Active Antiviral Compounds Against COVID-19 Disease Targeting Coronavirus Endoribonuclease Nendou/NSP15 Via Ligandbased Virtual Screening and Molecular Docking
Letters in Drug Design & Discovery