Abstract
Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations.
Keywords: Systems biology, Drug discovery, Chemoinformatics, Chemoproteomics, Chemogenomics, Genomics, Phenomics.
Current Topics in Medicinal Chemistry
Title:Systems Biology Approaches to a Rational Drug Discovery Paradigm
Volume: 16 Issue: 9
Author(s): Philip Prathipati and Kenji Mizuguchi
Affiliation:
Keywords: Systems biology, Drug discovery, Chemoinformatics, Chemoproteomics, Chemogenomics, Genomics, Phenomics.
Abstract: Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations.
Export Options
About this article
Cite this article as:
Prathipati Philip and Mizuguchi Kenji, Systems Biology Approaches to a Rational Drug Discovery Paradigm, Current Topics in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1568026615666150826114524
DOI https://dx.doi.org/10.2174/1568026615666150826114524 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1), a Relevant Target for Diabetic Vasculopathy?
Cardiovascular & Hematological Disorders-Drug Targets Metformin Beyond Diabetes: New Life for an Old Drug
Current Diabetes Reviews Genetic Determinants of HDL Metabolism
Current Medicinal Chemistry Beta-Blockers use for Hypertension in the Elderly
Cardiovascular & Hematological Agents in Medicinal Chemistry Diagnosis and Management of Chronic Coronary Artery Disease
Current Cardiology Reviews Biology and Clinical Relevance of Mannose-Binding Lectin
Drug Design Reviews - Online (Discontinued) Statins Exert Multiple Beneficial Effects on Patients Undergoing Percutaneous Revascularization Procedures
Current Drug Targets Editorial (Thematic Issue: Vascular Damage In Systemic Sclerosis)
Current Rheumatology Reviews Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment
Current Genomics Platelet Resistance to the Anti-Aggregating Agents in the Insulin Resistant States
Current Diabetes Reviews Pharmacogenetics and Anaesthesiology
Current Pharmacogenomics Subject Index To Volume 6
Current Molecular Medicine Insulin Resistance and Postprandial Hyperglycemia the Bad Companions in Natural History of Diabetes: Effects on Health of Vascular Tree
Current Diabetes Reviews Cardiovascular Disease: What's All the AGE/RAGE About?
Cardiovascular & Hematological Disorders-Drug Targets Natural Products as Anti-glycation Agents: Possible Therapeutic Potential for Diabetic Complications
Current Diabetes Reviews Nano-Systems for Advanced Therapeutics and Diagnosis of Atherosclerosis
Current Pharmaceutical Design Lipid-lowering Therapy in the Diabetic Foot: Seeing the Whole Iceberg and not Just the Tip
Current Vascular Pharmacology Erythropoiesis Stimulating Agents and Anaemia of End-Stage Renal Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Catastrophic Antiphospholipid Syndrome - 20 Years Later
Current Rheumatology Reviews Infection, its Treatment and the Risk for Stroke
Current Vascular Pharmacology