hERGK+ionchannelbinding钾离子通道结合分析.pdfVIP

High Throughput, Reliable, Cost-Effective Early Screening for Binding at the HERG Potassium Ion Channel + The HERG potassium ion channel conducts rapidly activating delayed rectifier K currents (I ) kr that critically contribute to cardiac repolarization. Mutations in the HERG (human ether-a-go- go) gene and drug-induced blockade of IKr currents have been linked to delayed repolarization of action potential resulting in prolonged QT interval. QT prolongation can lead to potentially lethal torsade de pointes, a form of polymorphic ventricular arrhythmia. Astemizole, terfena- dine, cisapride and grepafloxacin were recently withdrawn from the market due to torsade de pointes-related fatalities resulting from their inhibitory effects on the HERG channel. Inhibition Inhibition of of HERG is thus considered a significant risk factor against cardiac safety of new drugs and HERG is thus has become a subject under increased regulatory review. MDS Pharma Services’ HERG potas- sium ion channel binding assay has been developed and optimized to provide one of the considered a highest sensitivity HERG radioligand binding assays currently available. High correlations of significant risk affinity and rank order inhibition fr