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KCNH2 inhibits dofetilide. 3 / 3
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3
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"Of note, the similar levels of hERG potassium channel block induced by 2-3 nM dofetilide and 6.9 muM ranolazine (approximately 52%) induced> 200 ms of APDc and FPDc prolongation and multiple arrhythmic events in dofetilide treated cells, but only APDc and FPDc prolongation (< 150 ms) without arrhythmias in ranolazine treated cells."
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"To ensure that our model could perform for both drug-free and drugged iPSC-CM and adult-CM APs simultaneously, we simulated drugged samples via both a simple drug-induced I block model of hERG channel conduction, G , reduction by 1–50% and a complex Markov model of conformation-state dependent I block in the presence of a clinical concentration, 2.72 ng/mL, of a potent hERG blocking drug dofetilide from our recent study (Yang et al., 2020)."
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"Doxepin is quite distinct in this regard from a number of other drugs, including the archetypal high affinity HERG blocking methanesulphonanilide drugs E-4031 and dofetilide, for which I HERG inactivation exerts a strong influence on blocking potency - either as a direct consequence of inactivation-state dependent block, or due to conformational changes during inactivation facilitating optimal orientation of S6 helical residues to which drugs bind XREF_BIBR."