Optimizing the hERG Assay on the PatchXpress 7000A System for Compounds that Demonstrate Non-specific Binding

Abstract

Non-specific binding of compound can affect the potency measurement from both conventional and automated patch-clamp assays. Because of this, pre-cautions need to be taken to ensure this is minimized or eliminated. Eight compounds, astemizole, pimozide, dofetilide, cisapride, terfenadine, flunarizine, quinidine and imipramine were used to evaluate the effect of different assay conditions to overcome the effects of non-specific binding in our hERG assay on the PatchXpress 7000A system.

To achieve the best IC₅₀ values, in addition to optimizing instrument parameters to minimize non-specific binding, care had to be taken in all phases of compound preparation. Compound binding to plastic container need to be minimized. Buffers used for the assay also need to be optimized. In this poster, we present the assay conditions found that generated the best IC₅₀ values on the PatchXpress 7000A as well as the assay results for these compounds.