Protein binding-dependent decreases in hERG channel blocker potency assessed by whole-cell voltage clamp in serum.

@article{Margulis2010ProteinBD,
  title={Protein binding-dependent decreases in hERG channel blocker potency assessed by whole-cell voltage clamp in serum.},
  author={Michael Margulis and Steve Sorota and Inhou Chu and Anthony Soares and Tony Priestley and Amin A. Nomeir},
  journal={Journal of cardiovascular pharmacology},
  year={2010},
  volume={55 4},
  pages={368-76}
}
In vitro hERG blocking potency is measured in drug discovery as part of an integrated cardiovascular risk assessment. Typically, the concentrations producing 50% inhibition are measured in protein-free saline solutions and compared with calculated free therapeutic in vivo Cmax values to estimate a hERG safety multiple. The free/unbound fraction is believed responsible for activity. We tested the validity of this approach with 12 compounds by determining potencies in voltage clamp studies… CONTINUE READING