Abstract
Sudden death as a side effect of action of non-antiarrhythmic drugs is a major pharmacological safety concern facing the pharmaceutical industry and the health regulatory authorities. A number of drugs have been withdrawn from the market in recent years due to cardiovascular toxicity associated with undesirable blockade of hERG potassium channel. Pharmaceuticals of widely varying structure have been shown to interact with hERG. Defining the molecular features that confer hERG inhibitory activity has therefore become a focus of considerable computational and statistical modeling efforts. Some of the approaches are aimed primarily at filtering out potential hERG blockers in the context of virtual libraries, while others involve understanding structure-activity relationships governing hERG-drug interactions. The ability of models to produce structural hypotheses that can be tested by the project teams has become the key prerequisite driving their organization-wide adoption.
Keywords: hERG, QT prolongation, virtual screening, predictive ADMET, pharmacophore
Current Topics in Medicinal Chemistry
Title: Ligand Structural Aspects of hERG Channel Blockade
Volume: 8 Issue: 13
Author(s): Alex M. Aronov
Affiliation:
Keywords: hERG, QT prolongation, virtual screening, predictive ADMET, pharmacophore
Abstract: Sudden death as a side effect of action of non-antiarrhythmic drugs is a major pharmacological safety concern facing the pharmaceutical industry and the health regulatory authorities. A number of drugs have been withdrawn from the market in recent years due to cardiovascular toxicity associated with undesirable blockade of hERG potassium channel. Pharmaceuticals of widely varying structure have been shown to interact with hERG. Defining the molecular features that confer hERG inhibitory activity has therefore become a focus of considerable computational and statistical modeling efforts. Some of the approaches are aimed primarily at filtering out potential hERG blockers in the context of virtual libraries, while others involve understanding structure-activity relationships governing hERG-drug interactions. The ability of models to produce structural hypotheses that can be tested by the project teams has become the key prerequisite driving their organization-wide adoption.
Export Options
About this article
Cite this article as:
Aronov M. Alex, Ligand Structural Aspects of hERG Channel Blockade, Current Topics in Medicinal Chemistry 2008; 8 (13) . https://dx.doi.org/10.2174/156802608785700061
DOI https://dx.doi.org/10.2174/156802608785700061 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
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
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Peripartum Cardiomyopathy: An Intensivist's Perspective
Current Women`s Health Reviews Persistence of Trypanosoma cruzi in Experimental Chagasic Cardiomyopathy
Anti-Infective Agents Physical Function and Exercise in Older Patients with Cardiovascular and Respiratory Conditions
Current Pharmaceutical Design Drug Interactions between Non-Steroidal Anti-Inflammatory Drugs and Cardiovascular Treatments (Except Anti-Agregant Therapy)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Pharmacogenomic Considerations in the Treatment of the Pediatric Cardiomyopathy Called Barth Syndrome
Recent Patents on Biotechnology Methylene Blue and Vasoplegia: Who, When, and How?
Mini-Reviews in Medicinal Chemistry Impact of Novel Screening Technologies on Ion Channel Drug Discovery
Combinatorial Chemistry & High Throughput Screening A Brief History of ‘Lone’ Atrial Fibrillation: From ‘A Peculiar Pulse Irregularity’ to a Modern Public Health Concern
Current Pharmaceutical Design Application of Current Diagnostic Criteria for Arrhythmogenic Right Ventricular Cardiomyopathy in Every Day Clinical Practice
Current Pharmaceutical Design Anesthetic Cardioprotection: The Role of Adenosine
Current Pharmaceutical Design Beta-Blockers use for Hypertension in the Elderly
Cardiovascular & Hematological Agents in Medicinal Chemistry Association of Stress Hyperglycemia and Adverse Cardiac Events in Acute Myocardial Infarction - A Cohort Study
Cardiovascular & Hematological Disorders-Drug Targets Cardiotoxicity of Tyrosine-Kinase-Targeting Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Thyroid Hormones and Cardiovascular System: From Bench to Bedside
Current Drug Therapy Acetaminophen (Paracetamol) and Injury in the Cardiovascular System
Vascular Disease Prevention (Discontinued) Rate and Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation: Current Status
Current Cardiology Reviews Repositioning of Drugs in Cardiometabolic Disorders: Importance and Current Scenario
Current Topics in Medicinal Chemistry Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction
Current Pharmaceutical Design Pattern of Medication Use Among Older Inpatients in Seven Hospitals in Italy: Results from the Criteria to Assess Appropriate Medication Use Among Elderly Complex Patients (CRIME) Project
Current Drug Safety Investigating Drug-induced Mitochondrial Toxicity: A Biosensor to Increase Drug Safety?
Current Drug Safety