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
-
Perspectives in Therapeutic Innovation in Ocular Surface Disorders and Dry Eye Syndrome
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Renal Artery Stenting: Efficacy and Complications
Current Hypertension Reviews Type 1 Diabetes and Physical Exercise: Moving (forward) as an Adjuvant Therapy
Current Pharmaceutical Design Circadian Cycle and Chronotherapeutics: Recent Trend for the Treatment of Various Biological Disorders
Recent Patents on Drug Delivery & Formulation Sevoflurane in Intraoperative and Postoperative Cardiac Surgery Patients. Our Experience in Intensive Care Unit with Sevoflurane Sedation
Current Pharmaceutical Design Targeting the Brain: Advances in Drug Delivery
Current Pharmaceutical Biotechnology Managing Sleep Disturbance in Bipolar Disorder
Current Psychiatry Reviews PDE5 Inhibitors: In Vitro and In Vivo Pharmacological Profile
Current Pharmaceutical Design The Role of Inflammatory and Cytokine Biomarkers in the Pathogenesis of Frailty Syndrome
Endocrine, Metabolic & Immune Disorders - Drug Targets Review of Computer-Aided Models for Predicting Collagen Stability
Current Computer-Aided Drug Design Accessing the Blood-Brain Barrier to Treat Brain Disorders
Current Nanomedicine Advances in the Researches on the Biological Activities and Inhibitors of Phosphatidylinositol 3-kinase
Anti-Cancer Agents in Medicinal Chemistry Review of Recent Clinical Developments and Patents for the Treatment of Autoimmune and Inflammatory Diseases by Mesenchymal Stromal Cells
Recent Patents on Regenerative Medicine Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal
Current Pharmaceutical Design Myocardial Revascularization for the Elderly: Current Options, Role of Off-pump Coronary Artery Bypass Grafting and Outcomes
Current Cardiology Reviews The HCMV Chemokine Receptor US28 is a Potential Target in Vascular Disease
Current Drug Targets - Infectious Disorders The Effect of Nicotine and Tobacco on Aortic Matrix Metalloproteinases in the Production of Aortic Aneurysm
Current Vascular Pharmacology Coupling of Conjugating Enzymes and Efflux Transporters: Impact on Bioavailability and Drug Interactions
Current Drug Metabolism Protein Interaction Networks in Metallo Proteins and Docking Approaches of Metallic Compounds with TIMP and MMP in Control of MAPK Pathway
Letters in Drug Design & Discovery Roles of Adrenomedullin in Hypertension and Hypertensive Organ Damage
Current Hypertension Reviews