Abstract
Screening and identifying multi-target ligands becomes a daunting task when there are very few matching pharmacophoric features among the proteins. Herein, we describe a novel screening strategy to identify multi-target ligands for proteins having varying pharmacophoric features with their ligands. This strategy was adopted to identify multi-target ligands for death-associated protein kinase (DAPk) family. The role of the kinase activity of DAPk in eukaryotic cell apoptosis and the ability of bioavailable DAPk inhibitors to rescue neuronal death after brain injury have made it a drug-discovery target for neurodegenerative disorders. In this work, we employed a novel strategy using the existing computational approaches to design multi-target inhibitors, which can potentially inhibit one or any combination of the three DAPk family members. The strategy employs a combination of merged pharmacophore matching, database screening and molecular docking to reliably identify potential multi-target inhibitors targeted against DAPk protein family.
Keywords: DAPk1, DRP1, merged pharmacophore, multi-target, polypharmacology, ZIPk.
Combinatorial Chemistry & High Throughput Screening
Title:A Novel Multi-Target Drug Screening Strategy Directed Against Key Proteins of DAPk Family
Volume: 16 Issue: 6
Author(s): Syam B. Nair, Shaik M. Fayaz and Golgodu K. Rajanikant
Affiliation:
Keywords: DAPk1, DRP1, merged pharmacophore, multi-target, polypharmacology, ZIPk.
Abstract: Screening and identifying multi-target ligands becomes a daunting task when there are very few matching pharmacophoric features among the proteins. Herein, we describe a novel screening strategy to identify multi-target ligands for proteins having varying pharmacophoric features with their ligands. This strategy was adopted to identify multi-target ligands for death-associated protein kinase (DAPk) family. The role of the kinase activity of DAPk in eukaryotic cell apoptosis and the ability of bioavailable DAPk inhibitors to rescue neuronal death after brain injury have made it a drug-discovery target for neurodegenerative disorders. In this work, we employed a novel strategy using the existing computational approaches to design multi-target inhibitors, which can potentially inhibit one or any combination of the three DAPk family members. The strategy employs a combination of merged pharmacophore matching, database screening and molecular docking to reliably identify potential multi-target inhibitors targeted against DAPk protein family.
Export Options
About this article
Cite this article as:
B. Nair Syam, M. Fayaz Shaik and K. Rajanikant Golgodu, A Novel Multi-Target Drug Screening Strategy Directed Against Key Proteins of DAPk Family, Combinatorial Chemistry & High Throughput Screening 2013; 16 (6) . https://dx.doi.org/10.2174/1386207311316060005
DOI https://dx.doi.org/10.2174/1386207311316060005 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...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
Related Articles
-
The Protective Role of Heme Oxygenase-1 in Cerebral Ischemia
Central Nervous System Agents in Medicinal Chemistry Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study
Current Alzheimer Research A Therapeutic Target of Cerebral Hemorrhagic Stroke: Matrix Metalloproteinase- 9
Current Drug Targets Structural Characterization, Biological Effects, and Synthetic Studies on Xanthones from Mangosteen (Garcinia mangostana), a Popular Botanical Dietary Supplement
Mini-Reviews in Organic Chemistry Dissecting the Mechanisms of Thrombogenesis and Atherosclerosis for Neurodegenerative Disorders
Current Neurovascular Research Neurobehavioral and Cognitive Changes Induced by Hypoxia in Healthy Volunteers
CNS & Neurological Disorders - Drug Targets Regulation of Cl- Electrolyte Permeability in Epithelia by Active Traditional Chinese Medicine Monomers for Diarrhea
Current Drug Targets Cell Metabolism Under Microenvironmental Low Oxygen Tension Levels in Stemness, Proliferation and Pluripotency
Current Molecular Medicine Development of Therapeutics for High Grade Gliomas Using Orthotopic Rodent Models
Current Medicinal Chemistry Peptidyl Arginine Deiminases and Neurodegenerative Diseases
Current Medicinal Chemistry Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein 1: Recent Developments Concerning Substrates and Inhibitors of a Promising Therapeutic Target
Current Medicinal Chemistry Chelating Agents for Metal Intoxication
Current Medicinal Chemistry 18FDG-PET/CT in Traumatic Brain Injury Patients: The Relative Hypermetabolism of Vermis Cerebelli as a Medium and Long Term Predictor of Outcome
Current Radiopharmaceuticals Evaluation of the Effects of <i>Rumex obtusifolius</i> Seed and Leaf Extracts Against <i>Acanthamoeba</i>: An in vitro Study
Infectious Disorders - Drug Targets Targeting Drugs to APJ Receptor: The Prospect of Treatment of Hypertension and Other Cardiovascular Diseases
Current Drug Targets Platelets in Alzheimer’s Disease-Associated Cellular Senescence and Inflammation
Current Pharmaceutical Design Simvastatin and Other HMG-CoA Reductase Inhibitors on Brain Cholesterol Levels in Alzheimers Disease
Current Alzheimer Research Structural Design and Physicochemical Foundations of Hydrogels for Biomedical Applications
Current Medicinal Chemistry Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies
Current Gene Therapy Current and Future Therapeutic Strategies to Target Inflammation in Stroke
Current Drug Targets - Inflammation & Allergy