E-4031
Encyclopedia
E-4031 is an experimental class III antiarrhythmic drug that blocks potassium channel
s of the hERG-type
.
that is a methanesulfonanilide class III antiarrhythmic drug.
s mainly found in the heart, the hERG channels. hERG channels (Kv11.1) mediate the IKr current, which repolarizes the myocardial cells. The hERG channel is encoded by ether-a-go-go related gene (hERG).
Reducing IKr in myocardial cells prolongs the cardiac action potential
and thus prolongs the QT-interval
. In non-cardiac cells, blocking Ikr has a different effect: it increases the frequency of action potentials.
has been conducted to test the effect of E-4031 on prolongation of the QT-interval
.
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
s of the hERG-type
HERG
hERG is a gene that codes for a protein known as Kv11.1 potassium ion channel...
.
Chemistry
E-4031 is a synthetized toxinToxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
that is a methanesulfonanilide class III antiarrhythmic drug.
Target
E-4031 acts on a specific class of voltage-gated potassium channelVoltage-gated potassium channel
Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
s mainly found in the heart, the hERG channels. hERG channels (Kv11.1) mediate the IKr current, which repolarizes the myocardial cells. The hERG channel is encoded by ether-a-go-go related gene (hERG).
Mode of action
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 IKr in myocardial cells prolongs the cardiac action potential
Cardiac action potential
In electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....
and thus prolongs the QT-interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
. In non-cardiac cells, blocking Ikr has a different effect: it increases the frequency of action potentials.
Toxicity
As E-4031 can prolong the QT-interval, it can cause lethal arrhythmias.Therapeutic use
As of yet, E-4031 is solely used for research purposes. So far, one clinical trialClinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
has been conducted to test the effect of E-4031 on prolongation of the QT-interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
.