QPatch IC50 values for 32 unknown compounds provided by Aventis. The effects of the compounds were tested on whole-cell currents from CHO cells expressing hERG. In the original test, several compounds gave IC50 that were 5-15 times higher than those estimated by conventional patch-clamp (determined by Aventis). Because the compounds had been kept in plastic microtitre plates (MTPs) prior to the test, it was suggested that non-specific binding ('stickiness') could be the reason for the discrepancy. Consequently 11 of the compounds with markedly raised IC50 values were retested after being kept in glass-coated MTPs. These data are shown in the diagram.
.JPG)
Black points: 21 unknown compounds, original test (compounds kept in plastic-coated MTPs)
Blue points: 11 unknown compounds, retest (componds kept in glass-coated MTPs)
Green points: verapamil (patch-clamp values from Chouabe et al., Mol.Pharmacol., 54:695(1998), and Zhang et al., Circulation Res., 84:989(1999)
Red point: rBeKm-1 Patch-clamp value from Alomone (www.Alomone.com)
The diagram also includes IC50 values for two reference compounds (rBeKm-1 and verapamil).
As a mean the QPatch IC50 values are a factor 1.15 higher than the manually determined values. 59 % of the IC50 values were less than a factor of 2 from the manual patch clamp values, and 97 % of the IC50 values were less than a factor of 10 from the manual patch clamp.
Contact Frank Henrichsen, fhe@sophion.dk, to get the entire report.
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