Where is the hERG channel?

The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel, Kv11. 1, which are expressed in the heart, various brain regions, smooth muscle cells, endocrine cells, and a wide range of tumor cell lines.

What is a hERG channel blockers?

Introduction: The HERG channel is widely used for the assessment of proarrhythmic risk for new drugs. HERG channel blockers obstruct channel functions through various mechanisms, which usually show time dependence, voltage dependence, and state dependence.

Is hERG a voltage gated ion channel?

HERG, a human inward rectifier in the voltage-gated potassium channel family.

What is the hERG assay?

A hERG (human Ether-a-go-go Related Gene) assay is a laboratory technique that gauges the activity of the hERG channel protein. hERG activity manifests as the movement of potassium ions through a pore present in the hERG channel protein.

What is hERG liability?

Introduction. The inhibition of the human ether-a-go-go (hERG) ion channel may cause QT interval prolongation, which eventually can result in torsades de pointes (TdP) [1] and even death. Hence cardiotoxicity caused by the inhibition of hERG is a major liability within the drug development process.

What is the physiological role of hERG?

The human ether-à-go-go related gene (hERG; officially designated as KCNH2) encodes the structure of protein forming α-subunit of voltage-gated ion channel which conducts the rapid component of delayed rectifier K+ current (IKr). This current plays an important role namely in the cardiac repolarization.

What is hERG IC50?

The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (Cmax ) is used during drug development to screen out chemical entities likely to cause TdP.

What is the significance of hERG assay & QT prolongation studies?

The hERG and in vivo QT data, combined with the likely indication and the estimated free drug level for efficacy, are put together to assess the risk that the potential drug will prolong QT in man.

Why is hERG important?

The importance of the hERG ion channel for drug discovery programs stems from the observation that not only mutations, but also drug induced blockade of the channel, may cause repolarization abnormalities.

How can I reduce my hERG?

Introduction of an aliphatic oxygen near to an amine can significantly reduce HERG binding, as can be seen below this can be ascribed to a reduction on the pKa of the basic nitrogen, but also the hydroxyl serves to reduce the overall lipophilicity.

What is the function of the hERG ion channel?

This ion channel (sometimes simply denoted as ‘hERG’) is best known for its contribution to the electrical activity of the heart: the hERG channel mediates the repolarizing I Kr current in the cardiac action potential, which helps coordinate the heart’s beating.

What is the function of the hERG potassium channel?

the hERG potassium channel. HERG channels are involved in cardiac action potential repolarization, and reduced function of hERG lengthens ventricular action potentials, prolongs the QT interval in an electrocardiogram, and increases the risk for poten‑ tially fatal ventricular arrhythmias.

What is the function of the hERG gene?

hERG (the h uman Ether-à-go-go – R elated G ene) is a gene ( KCNH2) that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel (sometimes simply denoted as ‘hERG’) is best known for its contribution to the electrical activity of the heart: the hERG channel mediates the repolarizing IKr…

What is the function of the ion channel in the heart?

hERG forms the major portion of one of the ion channel proteins (the ‘rapid’ delayed rectifier current (IKr)) that conducts potassium (K+) ions out of the muscle cells of the heart, and this current is critical in correctly timing the return to the resting state of the cell membrane during the cardiac action potential.