Abstract
We describe the opportunities posed by computer-assisted drug design in the light of two aspects of the current drug discovery scenario: the decline of innovation due to high attrition rates at clinical stage of development and the combinatorial explosion emerging from exponential growth of feasible small molecules and genome and proteome exploration.
We present an overview of recent reports from our group in the field of rational drug development, by using topological descriptors (either alone, or in combination with different 3D approaches) and a diversity of modeling techniques such as Linear Discriminant Analysis and the Replacement Method. Modeling efforts aimed at the integrated prediction of several significant molecular properties in the field of drug discovery, such as pharmacological activity, aqueous solubility, human intestinal permeability and affinity to P-glycoprotein (ABCB1, MDR1) are reviewed. The suitability of conformation-independent descriptors to explore large chemical repositories is highlighted, as well as the opportunities posed by in silico guided drug repurposing.
Keywords: ADMET filters, classifiers, drug repurposing, linear models, QSAR, replacement method, topological descriptors, virtual screening, CNS disorders, high-throughput screening
Current Computer-Aided Drug Design
Title:An Integrated Drug Development Approach Applying Topological Descriptors
Volume: 8 Issue: 3
Author(s): Alan Talevi, Carolina L. Bellera, Mauricio Di Ianni, Pablo R. Duchowicz, Luis E. Bruno-Blanch and Eduardo A. Castro
Affiliation:
Keywords: ADMET filters, classifiers, drug repurposing, linear models, QSAR, replacement method, topological descriptors, virtual screening, CNS disorders, high-throughput screening
Abstract: We describe the opportunities posed by computer-assisted drug design in the light of two aspects of the current drug discovery scenario: the decline of innovation due to high attrition rates at clinical stage of development and the combinatorial explosion emerging from exponential growth of feasible small molecules and genome and proteome exploration.
We present an overview of recent reports from our group in the field of rational drug development, by using topological descriptors (either alone, or in combination with different 3D approaches) and a diversity of modeling techniques such as Linear Discriminant Analysis and the Replacement Method. Modeling efforts aimed at the integrated prediction of several significant molecular properties in the field of drug discovery, such as pharmacological activity, aqueous solubility, human intestinal permeability and affinity to P-glycoprotein (ABCB1, MDR1) are reviewed. The suitability of conformation-independent descriptors to explore large chemical repositories is highlighted, as well as the opportunities posed by in silico guided drug repurposing.
Export Options
About this article
Cite this article as:
Talevi Alan, L. Bellera Carolina, Di Ianni Mauricio, R. Duchowicz Pablo, E. Bruno-Blanch Luis and A. Castro Eduardo, An Integrated Drug Development Approach Applying Topological Descriptors, Current Computer-Aided Drug Design 2012; 8 (3) . https://dx.doi.org/10.2174/157340912801619076
DOI https://dx.doi.org/10.2174/157340912801619076 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
- 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
Related Articles
-
Development of PET Probes for Cancer Imaging
Current Topics in Medicinal Chemistry Preliminary Study on Major Phenolic Groups, Antioxidant and Cytotoxic Capacity of Tuckeroo (<i>Cupaniopsis Anacardioides</i>) Fruit Extracts
Current Nutraceuticals Hypoxic Tumor Microenvironment and Cancer Cell Differentiation
Current Molecular Medicine RNA Therapeutics Directed to the Non Coding Regions of APP mRNA, In Vivo Anti-Amyloid Efficacy of Paroxetine, Erythromycin, and N-acetyl cysteine
Current Alzheimer Research Alteration of Isocitrate Dehydrogenase Following Acute Ischemic Injury as a Means to Improve Cellular Energetic Status in Neuroadaptation
CNS & Neurological Disorders - Drug Targets Recent Approaches Targeting Beta-Amyloid for Therapeutic Intervention of Alzheimer's disease
Recent Patents on CNS Drug Discovery (Discontinued) Gynecomastia in Infants, Children, and Adolescents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Ouabain-Induced Signaling and Cell Survival in SK-N-SH Neuroblastoma Cells Differentiated by Retinoic Acid
CNS & Neurological Disorders - Drug Targets The Problem of Amino Acid Complementarity and Antisense Peptides
Current Protein & Peptide Science Current Non-viral Gene Therapy Strategies for the Treatment of Glioblastoma
Current Medicinal Chemistry Current Management of Neonatal Soft-tissue Sarcomas and Benign Tumors with Local Aggressiveness
Current Pediatric Reviews Lopinavir/Ritonavir Treatment Induces Oxidative Stress and Caspaseindependent Apoptosis in Human Glioblastoma U-87 MG Cell Line
Current HIV Research The Current Chemical Utility of Marine and Terrestrial Filamentous Fungi in Side-Chain Chemistry
Current Organic Chemistry Glycosylated Antitumor Ether Lipids: Activity and Mechanism of Action
Anti-Cancer Agents in Medicinal Chemistry Stem Cells: In Sickness and in Health
Current Stem Cell Research & Therapy Mitochondrial Permeability Transition as Target of Anticancer Drugs
Current Pharmaceutical Design Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Current Medicinal Chemistry Ethnobotanical Treatment Strategies Against Alzheimers Disease
Current Alzheimer Research New Insights in Mast Cell Modulation by Palmitoylethanolamide
CNS & Neurological Disorders - Drug Targets Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer
Current Drug Research Reviews