The blockage of the voltage dependent ion channel encoded by human ether-a-go-go related gene (hERG) may
lead to drug-induced QT interval prolongation, which is a critical side-effect of non-cardiovasular therapeutic agents.
Therefore, identification of potential hERG channel blockers at the early stage of drug discovery process will decrease the
risk of cardiotoxicity-related attritions in the later and more expensive development stage. Computational approaches provide
economic and efficient ways to evaluate the hERG liability for large-scale compound libraries. In this review, the
structure of the hERG channel is briefly outlined first. Then, the latest developments in the computational predictions of
hERG channel blockers and the theoretical studies on modeling hERG-blocker interactions are summarized. Finally, the
challenges of developing reliable prediction models of hERG blockers, as well as the strategies for surmounting these
challenges, are discussed.
Keywords: hERG, QT prolongation, ADME/T, QSAR, QSPR, homology modeling, pharmacophore modeling, molecular
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