Abstract
The human ether-a-go-go related gene (hERG) potassium channel is critical to the QT interval in the human heart measured by the electrocardiogram (ECG). The blockade of hERG would induce undesired lethal arrhythmia, named torsades de pointes (TdP), a rare but life-threatening symptom. Although a large number of experimental studies on hERG have been conducted so far, knowledge of how known ligands bind to hERG still remains sketchy and has been a major hindrance in the effort to designing novel medicinal molecules devoid of hERG activity in the hope of improving drug safety. This review summarizes several studies on ligand-hERG interactions by in silico receptor-based and ligand-based modeling approaches during recent years. These efforts could aid tremendously in understanding the determinants of ligand binding to hERG channel and the molecular basis of hERG channel blockade, and offer a more rational approach for the prediction of QT-prolongation liability and for the development of novel and safe non-cardiac agents.
Keywords: hERG potassium channel, ligand-based, non-cardiac agents, receptor-based
Current Topics in Medicinal Chemistry
Title: The Interactions Between hERG Potassium Channel and Blockers
Volume: 9 Issue: 4
Author(s): Lupei Du, Minyong Li and Qidong You
Affiliation:
Keywords: hERG potassium channel, ligand-based, non-cardiac agents, receptor-based
Abstract: The human ether-a-go-go related gene (hERG) potassium channel is critical to the QT interval in the human heart measured by the electrocardiogram (ECG). The blockade of hERG would induce undesired lethal arrhythmia, named torsades de pointes (TdP), a rare but life-threatening symptom. Although a large number of experimental studies on hERG have been conducted so far, knowledge of how known ligands bind to hERG still remains sketchy and has been a major hindrance in the effort to designing novel medicinal molecules devoid of hERG activity in the hope of improving drug safety. This review summarizes several studies on ligand-hERG interactions by in silico receptor-based and ligand-based modeling approaches during recent years. These efforts could aid tremendously in understanding the determinants of ligand binding to hERG channel and the molecular basis of hERG channel blockade, and offer a more rational approach for the prediction of QT-prolongation liability and for the development of novel and safe non-cardiac agents.
Export Options
About this article
Cite this article as:
Du Lupei, Li Minyong and You Qidong, The Interactions Between hERG Potassium Channel and Blockers, Current Topics in Medicinal Chemistry 2009; 9 (4) . https://dx.doi.org/10.2174/156802609788317829
DOI https://dx.doi.org/10.2174/156802609788317829 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...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
-
Levosimendan Preoperative
Current Pharmaceutical Design Opioids: Old Drugs for Potential New Applications
Current Pharmaceutical Design The Contemporary Management of Left Main Coronary Artery Disease
Current Cardiology Reviews Medicinal Plants with Multiple Effects on Cardiovascular Diseases: A Systematic Review
Current Pharmaceutical Design Editorial: Atrial Fibrillation after Coronary Surgery: The Need for an Effective Pharmacological Prophylaxis
Current Vascular Pharmacology Patent Annotations
Recent Patents on Cardiovascular Drug Discovery Research Toward Potassium Channels on Tumor Progression
Current Topics in Medicinal Chemistry Tuning hERG Out: Antitarget QSAR Models for Drug Development
Current Topics in Medicinal Chemistry Myocardial Regeneration: What is the Best Approach?
Current Cardiology Reviews Empirical Antimicrobial Therapy and QTc Interval Prolongation in Emergency Medicine
Current Drug Safety Antihypertensive Properties of Angiotensin-Converting Enzyme Inhibitors (ACEI) Independent of the Renin-Angiotensin System
Current Hypertension Reviews The Effect of Adult and Pediatric Cardiopulmonary Bypass on Pharmacokinetic and Pharmacodynamic Parameters
Current Clinical Pharmacology Molecular Replacement in Cancer Therapy: Reversing Cancer Metabolic and Mitochondrial Dysfunction, Fatigue and the Adverse Effects of Cancer Therapy
Current Cancer Therapy Reviews Prognostic Relevance of Metabolic Approach in Patients with Heart Failure
Current Pharmaceutical Design The Measurement of the QT Interval
Current Cardiology Reviews Editorial (Thematic Issue: Health Impact and Management of a Disrupted Circadian Rhythm and Sleep in Critical Illnesses)
Current Pharmaceutical Design Patent Selections
Recent Patents on Cardiovascular Drug Discovery Development of Novel Cardiovascular Therapeutics From Small Regulatory RNA Molecules - An Outline of Key Requirements
Current Pharmaceutical Design Remote Preconditioning- Endocrine Factors in Organ Protection Against Ischemic Injury
Endocrine, Metabolic & Immune Disorders - Drug Targets Reversal of Calcium Dysregulation as Potential Approach for Treating Alzheimer's Disease
Current Alzheimer Research