Abstract
During the past decade asialoglycoprotein receptor (ASGP-R) expressed predominantly by hepatocytes has attracted a considerable attention as a convenient biomolecular trap for targeted drug delivery. Currently, several selective galactose-containing ligands equipped by drug molecules, e.g. known anticancer therapeutics, as well as diagnostic tools are under active preclinical development. In this paper, we have carried out a rational in silico screening among the molecules available in ChemDiv collection and compounds provided by our colleagues to reveal potential ASGP-R binders. Thus, 3D molecular docking approach provided a set of 100 `high score` molecules that was subsequently evaluated in vitro using an advanced Surface Plasmon Resonance (SPR) technique. As a result, dozens of novel small-molecule ASGP-R ligands with high diversity in structure were identified. Several hits showed the binding affinity much more better than that determined for galactose and Nacetylgalactosamine which were used as reference compounds. The disclosed molecules can be reasonably regarded as promising molecular devices for targeted drug delivery to hepatocytes.
Keywords: Asialoglycoprotein receptor (ASGRP-R), drug delivery, docking, in silico, screening.
Current Drug Delivery
Title:Identification of Novel Small-Molecule ASGP-R Ligands
Volume: 13 Issue: 8
Author(s): Alexander G. Majouga, Yan A. Ivanenkov, Mark S. Veselov, Anton V. Lopuhov, Svetlana V. Maklakova, Elena K. Beloglazkina, Petr V. Binevski, Natalya L. Klyachko, Yuri B. Sandulenko, Natalia Y. Galkina and Victor E. Koteliansky
Affiliation:
Keywords: Asialoglycoprotein receptor (ASGRP-R), drug delivery, docking, in silico, screening.
Abstract: During the past decade asialoglycoprotein receptor (ASGP-R) expressed predominantly by hepatocytes has attracted a considerable attention as a convenient biomolecular trap for targeted drug delivery. Currently, several selective galactose-containing ligands equipped by drug molecules, e.g. known anticancer therapeutics, as well as diagnostic tools are under active preclinical development. In this paper, we have carried out a rational in silico screening among the molecules available in ChemDiv collection and compounds provided by our colleagues to reveal potential ASGP-R binders. Thus, 3D molecular docking approach provided a set of 100 `high score` molecules that was subsequently evaluated in vitro using an advanced Surface Plasmon Resonance (SPR) technique. As a result, dozens of novel small-molecule ASGP-R ligands with high diversity in structure were identified. Several hits showed the binding affinity much more better than that determined for galactose and Nacetylgalactosamine which were used as reference compounds. The disclosed molecules can be reasonably regarded as promising molecular devices for targeted drug delivery to hepatocytes.
Export Options
About this article
Cite this article as:
Majouga G. Alexander, Ivanenkov A. Yan, Veselov S. Mark, Lopuhov V. Anton, Maklakova V. Svetlana, Beloglazkina K. Elena, Binevski V. Petr, Klyachko L. Natalya, Sandulenko B. Yuri, Galkina Y. Natalia and Koteliansky E. Victor, Identification of Novel Small-Molecule ASGP-R Ligands, Current Drug Delivery 2016; 13 (8) . https://dx.doi.org/10.2174/1567201813666160719144651
DOI https://dx.doi.org/10.2174/1567201813666160719144651 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...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
-
Evaluation of In-Vitro Multidrug Resistance Reversal Activities of HZ08 analogues with Improved Soluble Property
Letters in Drug Design & Discovery Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches
Current Cancer Drug Targets Antibody-Based Preventive and Therapeutic Strategies Against HIV
Current HIV Research Interleukin-6: A Critical Cytokine in Cancer Multidrug Resistance
Current Pharmaceutical Design Lipid-Based Nanocarriers for RNA Delivery
Current Pharmaceutical Design Pediatric Immune Dysfunction and Health Risks Following Early-Life Immune Insult
Current Pediatric Reviews Angiogenesis Markers in Gynecological Tumors and Patents for Anti- Angiogenic Approach: Review
Recent Patents on Anti-Cancer Drug Discovery Understanding Cancer Drug Resistance by Developing and Studying Resistant Cell Line Models
Current Cancer Drug Targets Chalcones in Cancer: Understanding their Role in Terms of QSAR
Current Medicinal Chemistry Cancer Stem Cells – Are Surface Markers Alone Sufficient?
Current Stem Cell Research & Therapy Mechanistic and Clinical Aspects of Lenalidomide Treatment for Chronic Lymphocytic Leukemia
Current Cancer Drug Targets Isolation of Secreted microRNAs (miRNAs) from Cell-conditioned Media
MicroRNA Synthesis, In Vitro Anticancer, Anti-Inflammatory and DNA Binding Activity of Thiazolidinedione Derivatives
Anti-Cancer Agents in Medicinal Chemistry Protective Effect of Heat Shock Proteins in the Nervous System
Current Neurovascular Research Multi-target Drug Discovery via PTML Modeling: Applications to the Design of Virtual Dual Inhibitors of CDK4 and HER2
Current Topics in Medicinal Chemistry Polymeric Nanocarriers: New Endeavors for the Optimization of the Technological Aspects of Drugs
Recent Patents on Biomedical Engineering (Discontinued) Drug Transport Across the Blood-Brain Barrier and the Impact of Breast Cancer Resistance Protein (ABCG2)
Current Topics in Medicinal Chemistry The Influence of Wuzhi Capsule on the Pharmacokinetics of Cyclophosphamide
Recent Patents on Anti-Cancer Drug Discovery Specificity of Binding in Protein Kinases
Current Enzyme Inhibition Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
Current Medicinal Chemistry