E-4031

Names

[ Name ]:
E-4031

[Synonym ]:
Methanesulfonamide, N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl]-, hydrochloride (1:2)
N-[4-({1-[2-(6-Methyl-2-pyridinyl)ethyl]-4-piperidinyl}carbonyl)phenyl]methanesulfonamide dihydrochloride
E-4031
N-(4-(1-(2-(6-methylpyridin-2-yl)ethyl)piperidine-4-carbonyl)phenyl)methanesulfonamide dihydrochloride
N-[4-({1-[2-(6-Methylpyridin-2-yl)ethyl]piperidin-4-yl}carbonyl)phenyl]methanesulfonamide dihydrochloride
MFCD01754739
E 4031 dihydrochloride
PDZ1 Domain inhibitor peptide

Biological Activity

[Description]:

E-4031 is a benzenesulfonamide antiarrhythmic agent; blocks the ATP-sensitive potassium channel.IC50 value:Target: K+ channel blockerin vitro: Dofetilide and E-4031 induced EADs or TdP in all assays (50-83%), and the induction correlated with a significant increase in beat-to-beat variability of repolarization [1]. E-4031 (0.1 mumol/L) significantly prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced both the upstroke velocity of the action potential and the diastolic depolarization rate [2].in vivo: E-4031 in doses of 0.01 and 0.1 mg/kg that can provide the plasma concentrations effectively to inhibit IKrin vitro significantly delayed the repolarization beyond the initiation of diastole, resulting in the inversion of electro-mechanical coupling, which provides an ideal proarrhythmic substrate, while the durations of left ventricular systole and diastole remained the same [3]. Bepridil and E-4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia [4].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Cardiovascular Disease

[References]

[1]. Nalos L, et al. Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytes. Br J Pharmacol. 2012 Jan;165(2):467-78.

[2]. Verheijck EE, et al. Effects of delayed rectifier current blockade by E-4031 on impulse generation in single sinoatrial nodal myocytes of the rabbit. Circ Res. 1995 Apr;76(4):607-15.

[3]. Izumi-Nakaseko H, et al. Effects of selective IKr channel blockade by E-4031 on ventricular electro-mechanical relationship in the halothane-anesthetized dogs. Eur J Pharmacol. 2014 Oct 5;740:263-70.

[4]. Izumi D, et al. Effects of bepridil versus E-4031 on transmural ventricular repolarization and inducibility of ventricular tachyarrhythmias in the dog. Pacing Clin Electrophysiol. 2010 Aug;33(8):950-9.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
561.7ºC at 760 mmHg

[ Molecular Formula ]:
C₂₁H₂₉Cl₂N₃O₃S

[ Molecular Weight ]:
474.444

[ Flash Point ]:
293.5ºC

[ Exact Mass ]:
473.130676

[ PSA ]:
87.75000

[ LogP ]:
5.59460

[ Vapour Pressure ]:
1.21E-12mmHg at 25°C

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Articles

Kcnh2 and Kcnj8 interactively regulate skin wound healing and regeneration.

Wound Repair Regen. 23 , 797-806, (2015)

Previous studies indicate that ion channels are mediators of bioelectricity promoting wound closure/regeneration in nonmammalian, lower vertebrate systems. The role of ion channels however in regenera...

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

Anesthesiology 120(6) , 1400-13, (2014)

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct e...

Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.

Toxicol. Sci. 148 , 241-60, (2015)

More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Current in vitro testing strategies predominantly take the form...