E-4031

E-4031

Identifiers
IUPAC name N-[4-[1-[2-(6-Methylpyridin-2-yl)ethyl]piperidine-4-carbonyl]phenyl]
Synonyms	(1-[2-(6-methyl-2-pyridyl)ethyl]-4-(4-methylsulfonyl-aminobenzoyl)piperidine)
CAS Number	113558-89-7
PubChem CID	3185
IUPHAR/BPS	2605
ChemSpider	3073
ChEMBL	CHEMBL327980
Chemical and physical data
Formula	C21H27N3O3S
Molar mass	401.52 g/mol
3D model (Jmol)	Interactive image
SMILES Cc1cccc(n1)CCN2CCC(CC2)C(=O)c3ccc(cc3)NS(=O)(=O)C
InChI InChI=1S/C21H27N3O3S/c1-16-4-3-5-19(22-16)12-15-24-13-10-18(11-14-24)21(25)17-6-8-20(9-7-17)23-28(2,26)27/h3-9,18,23H,10-15H2,1-2H3 Key:SRUISGSHWFJION-UHFFFAOYSA-N

E-4031 is an experimental class III antiarrhythmic drug that blocks potassium channels of the hERG-type.

E-4031 is a synthetized toxin that is a methanesulfonanilide class III antiarrhythmic drug.

E-4031 acts on a specific class of voltage-gated potassium channels mainly found in the heart, the hERG channels. hERG channels (Kv11.1) mediate the I_Kr current, which repolarizes the myocardial cells. The hERG channel is encoded by ether-a-go-go related gene (hERG).

E-4031 blocks hERG-type potassium channels by binding to the open channels. Its structural target within the hERG-channel is unclear, but some other methanesulfonanilide class III antiarrhythmic drugs are known to bind to the S6 domain or C-terminal of the hERG-channel.

Reducing I_Kr in myocardial cells prolongs the cardiac action potential and thus prolongs the QT-interval. In non-cardiac cells, blocking I_kr has a different effect: it increases the frequency of action potentials.

As E-4031 can prolong the QT-interval, it can cause lethal arrhythmias.

E-4031 is solely used for research purposes. So far, one clinical trial has been conducted to test the effect of E-4031 on prolongation of the QT-interval.