Binding modes of hERG blockers: an unsolved mystery in the drug design arena

Figures & data

Figure 1. Structure of the hERG Channel. (a) Schematic representation of the hERG ‘channel pore’ (yellow circle) formed by four hERG subunits; (b) Cartoon representation of the cryo-EM structure of hERG showing the pore at the center formed by the four subunits (c*) Topology diagram of the hERG in lipid bilayer (only two subunits are shown for clarity); (d) Cartoon representation of two subunits of hERG cryo-EM structures; (e^Φ) Electrostatic potential map of the central cavity showing the lateral pockets (extended hydrophobic pockets) on either sides and (f) Zoomed view of the central cavity, selectivity filter (SF) and the two aromatic residues. Full color available online.

*Reprinted from [2] with permission of John Wiley and Sons.

^ΦReprinted from [17] with permission of Elsevier.

Kalyaanamoorthy S, Barakat KH. Development of safe drugs: the hERG challenge. Med Res Rev. Forthcoming 2017. DOI:10.1002/med.21445.

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