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
-
Potential Role of Acrolein in Neurodegeneration and in Alzheimers Disease
Current Molecular Pharmacology Hydroxamic Acids as Pharmacological Agents: An Update
Medicinal Chemistry Reviews - Online (Discontinued) Beyond Hemostasis: The Role of Platelets in Inflammation, Malignancy and Infection
Cardiovascular & Hematological Disorders-Drug Targets Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target
Current Pharmaceutical Design Circulating Levels of Soluble Angiogenic Factors in Multiple Myeloma: Correlation with Parameters of Disease Activity and Prognosis
Current Angiogenesis (Discontinued) Biochemistry and Neurobiology of Prosaposin: A Potential Therapeutic Neuro-Effector
Central Nervous System Agents in Medicinal Chemistry Mitochondrially-Targeted Therapeutic Strategies for Alzheimer’s Disease
Current Alzheimer Research A Quantitative Proteomic Analysis to Reveal Effects of N-acetylcysteine on H<sub>2</sub>O<sub>2</sub>-induced Cytotoxicity
Current Proteomics EZN-2208 (PEG-SN38), A 40 kDa Polyethylene Glycol (PEG) Conjugate, As an Anticancer Agent: Review of Preclinical and Clinical Data
Current Bioactive Compounds The Identification and Characterization of Excitotoxic Nerve-endings in Alzheimer Disease
Current Alzheimer Research The Gene Expression Profiles of Medulloblastoma Cell Lines Resistant to Preactivated Cyclophosphamide
Current Cancer Drug Targets Pleiotropic Effects of Cardioactive Glycosides
Current Medicinal Chemistry Targeting the Resistance of Pancreatic Cancer Cells to Nutrient Deprivation: Anti-Austerity Compounds
Current Drug Delivery Design, Synthesis and Evaluation of 8-Thiosubstituted 1,3,7- Trimethylxanthine Hydrazones with In-vitro Neuroprotective and MAO-B Inhibitory Activities
Medicinal Chemistry Calcitonin-Derived Carrier Peptides
Current Pharmaceutical Design Inhibition of Autophagy Strengthens Celastrol-Induced Apoptosis in Human Pancreatic Cancer In Vitro and In Vivo Models
Current Molecular Medicine Arginine Deprivation as a Targeted Therapy for Cancer
Current Pharmaceutical Design A New Target for Diagnosis and Treatment of CNS Disorders: Agmatinergic System
Current Medicinal Chemistry Crocetin: an Agent Derived from Saffron for Prevention and Therapy for Cancer
Current Pharmaceutical Biotechnology AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species
Current Pharmaceutical Design