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 A number of drugs have been withdrawn from the market in recent years due to cardiovascular toxicity associated with undesirable blockade of hERG potassium channel.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 A number of drugs have been withdrawn from the market in recent years due to cardiovascular toxicity associated with undesirable blockade of hERG potassium channel.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
-
Quantitative Analysis in Cardiovascular Imaging: Current Status
Current Medical Imaging The Cyclodextrin Sugammadex and Anaphylaxis to Rocuronium: Is Rocuronium Still Potentially Allergenic in the Inclusion Complex Form?
Mini-Reviews in Medicinal Chemistry Editorial: Pharmacological Therapy to Prevent Sudden Cardiac Death: Indications and Limitations in the Era of Devices
Mini-Reviews in Medicinal Chemistry Patent Selections
Recent Patents on Cardiovascular Drug Discovery Cardiac (myo)fibroblast: Novel Strategies for its Targeting Following Myocardial Infarction
Current Pharmaceutical Design Common Comorbidities that Alter Heart Failure Prognosis - Shaping New Thinking for Practice
Current Cardiology Reviews Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure
Current Pharmaceutical Design Editorial [Hot Topic: Membrane Channels as Therapeutic Targets (Executive Editor: Jean-Claude Herve)]
Current Pharmaceutical Design Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
Current Drug Targets MicroRNAs as Biomarkers in Hypertrophic Cardiomyopathy: Current State of the Art
Current Medicinal Chemistry Biomarkers in Atrial Fibrillation and Heart Failure
Current Medicinal Chemistry Challenges in Chagas Disease Drug Discovery: A Review
Current Medicinal Chemistry Antihypertensive Therapy: Role of Aldosterone Antagonists
Current Pharmaceutical Design Treating COPD in Older and Oldest Old Patients
Current Pharmaceutical Design Diabetic Peripheral Neuropathy: Diagnosis and Treatment
Current Drug Safety Pharmacological Regulators of Intracellular Calcium Release Channels
Current Pharmaceutical Design Are the Antioxidant Properties of Carvedilol Important for the Protection of Cardiac Mitochondria?
Current Vascular Pharmacology Xanthine Derivatives in the Heart: Blessed or Cursed?
Current Medicinal Chemistry Cytochrome P450 2C8 and Drug Metabolism
Current Topics in Medicinal Chemistry Present Insights on Cardiomyopathy in Diabetic Patients
Current Diabetes Reviews