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Common Pharmacophores for Uncharged Human Ether-a-go-go-Related Gene (hERG) Blockers

2006; American Chemical Society; Volume: 49; Issue: 23 Linguagem: Inglês

10.1021/jm060500o

1520-4804

Alex M. Aronov,

Receptor Mechanisms and Signaling

In silico approaches are widely used to predict human ether-a-go-go-related gene (hERG) channel blockade. Published pharmacophore models of hERG blockers typically contain a basic nitrogen center flanked by aromatic or hydrophobic groups. However, hERG blockade has been observed in series lacking the basic nitrogen. By utilizing screening data for 194 potent uncharged hERG actives, we propose a pharmacophore for neutral hERG blockers, and provide guidance on eliminating hERG liability in an uncharged hERG active chemical series.