Abstract
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively acting multifunctional serine/threonine kinase, a role of which has been marked in several physiological pathways, making it a potential target for the treatment of many diseases, including Type-II diabetes and Alzheimer’s. Design of GSK-3β selective inhibitor was the key challenge which led to the use of rational approaches like structure based methods (molecular docking), and ligand based methods (QSAR, pharmacophore mapping) studies. These methods provide insights into the enzyme–ligand interactions and structure activity relationship of different sets of compounds for the design of promising GSK-3 inhibitors. Molecular dynamic simulation studies have additionally been performed to address key issues like the unique requirement of prime phosphorylation of its substrate at P+4 by GSK-3β. An allosteric site has also been reported, where the binding of the peptide leads to the stabilization of the activation loop, resulting in the enhancement of the catalysis of enzymes. These studies are becoming useful in the design of therapeutically active discriminatory GSK-3 inhibitors. In this article, we present a review of recent efforts and future opportunities for the design of selective GSK-3β inhibitors.
Keywords: Glycogen synthase kinase-3, inhibitors design, rationale approaches, selectivity, type-ii diabetes, Alzheimer’s disease, ATP competitive inhibitors, Substrate competitive inhibitors.
Current Pharmaceutical Design
Title:Design of Glycogen Synthase Kinase-3 Inhibitors: An Overview on Recent Advancements
Volume: 19 Issue: 26
Author(s): Minhajul Arfeen and Prasad V. Bharatam
Affiliation:
Keywords: Glycogen synthase kinase-3, inhibitors design, rationale approaches, selectivity, type-ii diabetes, Alzheimer’s disease, ATP competitive inhibitors, Substrate competitive inhibitors.
Abstract: Glycogen Synthase Kinase-3 (GSK-3) is a constitutively acting multifunctional serine/threonine kinase, a role of which has been marked in several physiological pathways, making it a potential target for the treatment of many diseases, including Type-II diabetes and Alzheimer’s. Design of GSK-3β selective inhibitor was the key challenge which led to the use of rational approaches like structure based methods (molecular docking), and ligand based methods (QSAR, pharmacophore mapping) studies. These methods provide insights into the enzyme–ligand interactions and structure activity relationship of different sets of compounds for the design of promising GSK-3 inhibitors. Molecular dynamic simulation studies have additionally been performed to address key issues like the unique requirement of prime phosphorylation of its substrate at P+4 by GSK-3β. An allosteric site has also been reported, where the binding of the peptide leads to the stabilization of the activation loop, resulting in the enhancement of the catalysis of enzymes. These studies are becoming useful in the design of therapeutically active discriminatory GSK-3 inhibitors. In this article, we present a review of recent efforts and future opportunities for the design of selective GSK-3β inhibitors.
Export Options
About this article
Cite this article as:
Arfeen Minhajul and Bharatam V. Prasad, Design of Glycogen Synthase Kinase-3 Inhibitors: An Overview on Recent Advancements, Current Pharmaceutical Design 2013; 19 (26) . https://dx.doi.org/10.2174/1381612811319260007
DOI https://dx.doi.org/10.2174/1381612811319260007 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Cushing's Syndrome and Steroid Dementia
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Mesenchymal Stem Cells in Cartilage Regeneration
Current Stem Cell Research & Therapy Cytochrome P450 in Neurological Disease
Current Drug Metabolism New Trends in Analysis of Biopharmaceutical Products
Current Pharmaceutical Analysis Specific TNF-alpha Inhibition in Cerebral Aneurysm formation and Subarachnoid Hemorrhage
Current Drug Safety Effects of ACE Inhibitors on Skeletal Muscle
Current Pharmaceutical Design Treatment of Leishmaniasis: A Review and Assessment of Recent Research
Current Pharmaceutical Design Niacin Status, NAD Distribution and ADP-Ribose Metabolism
Current Pharmaceutical Design Pharmacological Aspects of the Enzastaurin-Pemetrexed Combination in Non-Small Cell Lung Cancer (NSCLC)
Current Drug Targets Glycolipids: Isolated from <i>Oplismenus burmannii</i> Induce Glucose Uptake in L6-GLUT4myc Myotube Cells
Current Topics in Medicinal Chemistry Neurodegenerative Disease: A Perspective on Cell-Based Therapy in the New Era of Cell-Free Nano-Therapy
Current Pharmaceutical Design Effects of Dietary Iron Modulation on Gut Microbial Composition and Function in Monogastrics: A Review
Protein & Peptide Letters Preliminary Pharmacological Screening of Anti-Hyperlipidemic Polyphyto Combination by Novelistic Highthroughput Screening Method
Current Bioactive Compounds Immunological Modulation by Lidocaine-Epinephrine and Prilocaine- Felypressin on the Functions Related to Natural Immunity in Neutrophils and Macrophages
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Carbon-based Nanomaterials: Carbon Nanotubes, Graphene, and Fullerenes for the Control of Burn Infections and Wound Healing
Current Pharmaceutical Biotechnology Pericyte: Potential Target for Hemorrhagic Stroke Prevention and Treatment
Current Drug Delivery An Overview of Innovations in Analysis and Beneficial Health Effects of Wine Polyphenols
Mini-Reviews in Medicinal Chemistry Oakmoss Exhibits Antihyperglycemic Activity in Streptozotocin-Induced Diabetic Rats
Cardiovascular & Hematological Disorders-Drug Targets β-Amyloid, Cholinergic Transmission, and Cerebrovascular System - A Developmental Study in a Mouse Model of Alzheimer's Disease
Current Pharmaceutical Design The Involvement of Blood Coagulation Factor XIII in Fibrinolysis and Thrombosis
Cardiovascular & Hematological Agents in Medicinal Chemistry