Description
E-4031 (113558-89-7) is a selective hERG potassium channel blocker. Inhibits the rapid delayed-rectifier K+ current (IKr). Class III antiarrhythmic agent. Cell permeable.
Uses
E-4031 free base is a selective hERG potassium channel blocker for use in class III anti-arrhythmic studies[1].
Definition
ChEBI: E-4031 is a sulfonamide.
in vitro
it has been reported that e-4031 could induce eads or tdp, and such induction correlated with a significant increase in variability of repolarization. in addition, e-4031 at 0.1 um was able to significantly prolong cycle length, action potential duration, and depolarized maximum diastolic potential. e-4031could also reduce the upstroke velocity of the action potential as well as the diastolic depolarization rate [1].
in vivo
animal study showed that e-4031 at 0.01 and 0.1 mg/kg could provide effective in-vitro plasma concentrations to significantly inhibit ikr and thus delayed the repolarization beyond the initiation of diastole, leading to the inversion of electro-mechanical coupling, which provides an ideal proarrhythmic substrate [2]. another sutdy found that e-4031 could prolong qt interval and ari in all lv layers, though the magnitude of prolongation was greatest in mid, particularly during bradycardia [3].
References
[1] E. FICKER. The Binding Site for Channel Blockers That Rescue Misprocessed Human Long QT Syndrome Type 2 ether-a-gogo-related Gene (HERG) Mutations*[J]. The Journal of Biological Chemistry, 2002, 122 1: 4989-4998. DOI:
10.1074/jbc.m107345200[2] E WETTWER. Effects of the new class III antiarrhythmic drug E-4031 on myocardial contractility and electrophysiological parameters.[J]. Journal of Cardiovascular Pharmacology, 1991, 17 3: 480-487. DOI:
10.1097/00005344-199103000-00018
![N-[4-[[1-[2-(6-METHYL-2-PYRIDINYL)ETHYL]-4-PIPERIDINYL]CARBONYL]PHENYL]METHANESULFONAMIDE DIHYDROCHLORIDE Structure](https://www.chemicalbook.com/CAS/GIF/113558-89-7.gif)