Computational models for cardiotoxicity via hERG inhibition
Cardiovascular disease is the leading cause of death for people of most ethnicities in the United States. The hERG potassium channel plays a pivotal role in cardiac rhythm regulation, and drug molecules and environmental chemicals can potentially induce cardiotoxicity via hERG inhibition. An evaluation of the effect of environmental chemicals on hERG channel function can help inform the potential public health risks of these compounds. NICEATM and NCATS scientists employed several machine-learning approaches to develop QSAR prediction models for the assessment of hERG inhibition for drug-like and environmental chemicals screened in the Tox21 federal research program (Krishna et al. 2022). The data and scripts used to generate the hERG prediction models are provided in an open-access format as key in vitro and in silico tools that can be applied in a translational toxicology pipeline for drug development and environmental chemical screening.