Abstract
Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design.
Keywords: Allo-network drugs, allosteric drugs, interactome, protein-protein interaction networks, protein structure networks, signaling networks
Current Topics in Medicinal Chemistry
Title:Allo-Network Drugs: Extension of the Allosteric Drug Concept to Protein- Protein Interaction and Signaling Networks
Volume: 13 Issue: 1
Author(s): Andras Szilagyi, Ruth Nussinov and Peter Csermely
Affiliation:
Keywords: Allo-network drugs, allosteric drugs, interactome, protein-protein interaction networks, protein structure networks, signaling networks
Abstract: Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design.
Export Options
About this article
Cite this article as:
Szilagyi Andras, Nussinov Ruth and Csermely Peter, Allo-Network Drugs: Extension of the Allosteric Drug Concept to Protein- Protein Interaction and Signaling Networks, Current Topics in Medicinal Chemistry 2013; 13 (1) . https://dx.doi.org/10.2174/1568026611313010007
DOI https://dx.doi.org/10.2174/1568026611313010007 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
Clear Cell Renal Cell Cancer Tumor-Propagating Cells: Molecular Characteristics
Current Signal Transduction Therapy mPEG-PLA Micelle for Delivery of Effective Parts of Andrographis Paniculata
Current Drug Delivery Meet Our Editorial Board Member
Recent Patents on Anti-Cancer Drug Discovery MDR1/P-Glycoprotein (ABCB1) as Target for RNA Interference-Mediated Reversal of Multidrug Resistance
Current Drug Targets Signaling Intermediates (PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK Pathways) as Therapeutic Targets for Anti-Cancer and Anti-Angiogenesis Treatments
Current Signal Transduction Therapy Advances in the Analysis of Hepatitis C Virus Specific T Cell Responses
Mini-Reviews in Medicinal Chemistry Challenges and Opportunities from Basic Cancer Biology for Nanomedicine for Targeted Drug Delivery
Current Cancer Drug Targets WNT4 Signaling in Female Gonadal Development
Endocrine, Metabolic & Immune Disorders - Drug Targets Abrogation of the G2 Checkpoint by Inhibition of Wee-1 Kinase Results in Sensitization of p53-Deficient Tumor Cells to DNA-Damaging Agents
Current Clinical Pharmacology Pharmaceutical Polymeric Nanoparticles Prepared by the Double Emulsion- Solvent Evaporation Technique
Recent Patents on Drug Delivery & Formulation Targeting MUC15 Protein in Cancer: Molecular Mechanisms and Therapeutic Perspectives
Current Cancer Drug Targets Research Progress on the Mechanisms of Combined Bevacizumab and Radiotherapy
Recent Patents on Anti-Cancer Drug Discovery Editorial [Personalized Vaccines and Public Health Genomics: Anticipating and Monitoring the ELSIs]
Current Pharmacogenomics and Personalized Medicine A synopsis on the linkage between age-related dementias and vascular disorders
CNS & Neurological Disorders - Drug Targets In Silico Prediction of Novel Inhibitors of the DNA Binding Activity of FoxG1
Medicinal Chemistry Antibodies As Promising Novel Neuroprotective Agents in the Central Nervous System Injuries
Central Nervous System Agents in Medicinal Chemistry The Use of Keratin in Biomedical Applications
Current Drug Targets Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms
Mini-Reviews in Medicinal Chemistry The Effects of Drug Metabolizing Enzyme Inhibitors on Hepatic Efflux and Uptake Transporters
Drug Metabolism Letters Protein Biomarkers in Cancers of the Digestive Tract - a Step Towards Personalized Medicine
Current Proteomics