Abstract
A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.
Keywords: Statistical molecular design, quantitative structure-activity relationship, factorial design, D-optimal design, Principal Component Analysis, library design, drug design, parallel synthesis
Current Medicinal Chemistry
Title: Statistical Molecular Design of Balanced Compound Libraries for QSAR Modeling
Volume: 17 Issue: 19
Author(s): A. Linusson, M. Elofsson, I.E. Andersson and M.K. Dahlgren
Affiliation:
Keywords: Statistical molecular design, quantitative structure-activity relationship, factorial design, D-optimal design, Principal Component Analysis, library design, drug design, parallel synthesis
Abstract: A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.
Export Options
About this article
Cite this article as:
Linusson A., Elofsson M., Andersson I.E. and Dahlgren M.K., Statistical Molecular Design of Balanced Compound Libraries for QSAR Modeling, Current Medicinal Chemistry 2010; 17 (19) . https://dx.doi.org/10.2174/092986710791233661
DOI https://dx.doi.org/10.2174/092986710791233661 |
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
-
Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs
Current Medicinal Chemistry An Efficient One-Step Synthesis of 1H-pyrazolo[3,4-b]pyridines in Basic Ionic Liquid [bmim]OH
Letters in Organic Chemistry Advancing Metabolomics Research and Biomarker Application with Nanotechnology
Current Metabolomics New Zinc Binding Motifs in the Design of Selective Carbonic Anhydrase Inhibitors
Mini-Reviews in Medicinal Chemistry Destination Penis? Gene Therapy as a Possible Treatment for Erectile Dysfunction
Current Gene Therapy Thrombotic Microangiopathies: Towards a Pathophysiology-Based Classification
Cardiovascular & Hematological Disorders-Drug Targets Sleep and Circadian Profiles of Bipolar Disorder: From Chronobiology to Novel Therapeutic Strategies
Current Psychiatry Reviews Non-Analgesic Effects of Opioids: Opioids’ Effects on Sleep (Including Sleep Apnea)
Current Pharmaceutical Design Current Evidence and Potential Mechanisms of Therapeutic Action of PEDF in Cervical Cancer Treatment
Current Molecular Medicine Expression of Heme Oxygenase-1 in Response to Proteasomal Inhibition
Protein & Peptide Letters Executive Functioning in Alcohol Use Studies: A Brief Review of Findings and Challenges in Assessment
Current Drug Abuse Reviews The Role of Vascular Endothelial Growth Factor Gene as the Genetic Marker of Atherothrombotic Disorders and in the Gene Therapy of Coronary Artery Disease
Cardiovascular & Hematological Agents in Medicinal Chemistry Role of Infrared Spectroscopy in Medicinal Plants Research in Pakistan
Current Bioactive Compounds Managing Skin Malignancies- How Family Doctors, Plastic Surgeons, and Dermatologists Can Help
Current Cancer Therapy Reviews Nucleic Acids Electro-transfer: From Bench to Bedside
Current Drug Metabolism Allosteric Modulation of Nicotinic Acetylcholine Receptors: The Concept and Therapeutic Trends
Current Pharmaceutical Design Clinical and Pre-clinical Applications of the Transcendental Meditation Program® in the Prevention and Treatment of Essential Hypertension and Cardiovascular Disease in Youth and Adults
Current Hypertension Reviews Innate Immune System Modulation During Aging: Contributions of Macrophages and Dendritic Cells
Current Immunology Reviews (Discontinued) Effects of Benzodiazepine and Pilocarpine on Rat Parotid Glands: Histomorphometric And Sialometric Study
Medicinal Chemistry Therapeutic Drugs in Bone Loss-Associated Disorders: Clinical Outcomes and Challenges
Current Drug Targets