LUF7244, an allosteric modulator/activator of K_v 11.1 channels, counteracts dofetilide-induced torsades de pointes arrhythmia in the chronic atrioventricular block dog model.

ABSTRACT:

Background and purpose

K_v 11.1 (hERG) channel blockade is an adverse effect of many drugs and lead compounds, associated with lethal cardiac arrhythmias. LUF7244 is a negative allosteric modulator/activator of K_v 11.1 channels that inhibits early afterdepolarizations in vitro. We tested LUF7244 for antiarrhythmic efficacy and potential proarrhythmia in a dog model.

Experimental approach

LUF7244 was tested in vitro for (a) increasing human I_Kv11.1 and canine I_Kr and (b) decreasing dofetilide-induced action potential lengthening and early afterdepolarizations in cardiomyocytes derived from human induced pluripotent stem cells and canine isolated ventricular cardiomyocytes. In vivo, LUF7244 was given intravenously to anaesthetized dog

SUBMITTER: Qile M 

PROVIDER: S-EPMC6780032 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature