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One of the typical ion channels used in safety pharmacology
is the hERG channel. A high percentage of hERG channel blockers
are considered to be 'sticky' compounds, which often adhere to
plastic surfaces. Due to the careful design of the NPC-1
chip, the test compounds only touch the glass surface during
the experiment. Therefore the risk of losing compound is
kept to a minimum.
The figures below show recordings from hERG channels expressed
in CHO cells. Both figures display the typical IV-relationship.
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One standard compound to block hERG channels is Terfenadine.
Since it is known to bind to plastic surfaces, the solutions
were prepared in glass containers. Four different concentrations
of Terfenadine were applied to the same cell. The corresponding
Hill fit is displayed on the right with a resulting IC50
= 22 ± 9 nM (n = 4).
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Two more compounds were tested on HEK293 cells expressing
the hERG channel.
The first compound is Cisapride and the corresponding Hill
fit is displayed on the left. The resulting IC50
= 5.5 ± 1.9 nM (n = 6), corresponding well to values reported in the literature, which range from 5 – 60 nM. Five different concentrations
were applied to the same cell.
The figure on the right shows the Hill fit of Flunarizine blocking
hERG channels. The IC50 = 249 ± 57 nM
(n = 4), in agreement with the value reported in the literature ( 344 nM).
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