Ligand Structural Aspects of hERG Channel Blockade

Author(s): Alex M. Aronov

Journal Name: Current Topics in Medicinal Chemistry

Volume 8 , Issue 13 , 2008

Become EABM
Become Reviewer


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 A number of drugs have been withdrawn from the market in recent years due to cardiovascular toxicity associated with undesirable blockade of hERG potassium channel.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

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2008
Page: [1113 - 1127]
Pages: 15
DOI: 10.2174/156802608785700061
Price: $65

Article Metrics

PDF: 18