The voltage-gated potassium channel encoded by hERG carries a delayed rectifying potassium current (IKr) underlying repolarization of the cardiac action potential. Pharmacological blockade of the hERG channel results in slowed repolarization and therefore prolongation of action potential duration and an increase in the QT interval as measured on an electrocardiogram. Those are possible to cause sudden death, leading to the withdrawals of many drugs, which is the reason for hERG screening. Computational in silico prediction models provide a rapid, economic way to screen compounds during early drug discovery. In this review, hERG prediction models are classified as 2D and 3D quantitative structure–activity relationship models, pharmacophore models, classification models, and structure based models (using homology models of hERG).

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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The authors thank D Hall and F Lombardo for valuable feedback.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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In silico prediction of hERG inhibition

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