title: Development and evaluation of high throughput functional assay methods for HERG potassium channel.
abstract: Three functional hERG channel assay methods have been developed and evaluated. The methods were tested against five known hERG channel inhibitors: dofetilide, terfenadine (Seldane), sertindole (Serdolect), astemizole (Hismanal), and cisapride (Propulsid). The DiBAC4(3)-based assays were found to be the most economical but had high false-hit rates as a result of the interaction of dye with the test compounds. The membrane potential dye assay had fewer color-quenching problems but was expensive and still gave false hits. The nonradioactive Rb+ efflux assay was the most sensitive of all the assays evaluated and had the lowest false-hit rate.
authors.affiliation: Department of Profiling and High Throughput Screening, Aventis Pharmaceuticals, Bridgewater, NJ 08807-2854, USA. weimin.tang@aventis.com
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: J
authors.initials: J
authors.lastname: Kang
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: D
authors.initials: D
authors.lastname: Rampe
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: D
authors.initials: D
authors.lastname: Dunnington
authors.forename: T
authors.initials: T
authors.lastname: Garyantes
mesh_terms: D000818:Animals; D016466:CHO Cells; D027682:Cation Transport Proteins; D003116:Color; D006224:Cricetinae; D051638:Ether-A-Go-Go Potassium Channels; D008564:Membrane Potentials; D008722:Methods; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012413:Rubidium / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012413:Rubidium