For seven of these drugs, their interactions with hERG were predicted in the top 20 list.
For three drugs, terfenadine, Sparfloxacin, Droperidol, their interactions with hERG were even ranked at the first place.
For analysis of KCNE interaction with HERG we generated a cell line that stably expresses HERG with the c-myc immmunoepitope engineered onto the C-terminus previously described [16].
Our results show that in the HEK heterologous expression system KCNE1 associates with HERG more robustly than KCNE2.
Systemic treatment of cancers with hERG antagonists may affect cardiac myocytes, resulting in apoptosis and heart failure.
Injection of cancer cells that were pretreated with hERG siRNA significantly attenuated tumorigenesis, confirming the pathological significance of hERG in tumor growth and suggesting a potential novel target in anticancer therapy (see below).
hERG current was measured in HEK293 cells, stably transfected with hERG channels; action potential duration (APD) and arrhythmogenic effects were measured in isolated Purkinje fibres and perfused hearts from rabbits.
Arsenic interferes with hERG trafficking to the cell surface by inhibiting hERG-chaperone complexes and increasing calcium currents as shown in a series of biochemical and electrophysiological experiments in vitro (Ficker et al. 2004).
hERGAPDbase is a web-based interface, which allows the user to search for chemical compounds with hERG channel-blocking potential and APD prolongation activity.
Modifications to the pyridazinone portion of the core and linker led to the identification of molecules with excellent target potency and selectivity with improved rat pharmacokinetic properties and reduced potential hERG liabilities.
