What does the hERG channel do?
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 current in the cardiac action potential, which helps coordinate the heart’s beating.
What is hERG channel inhibition?
The hERG channel inhibition assay is a highly sensitive measurement which will identify compounds exhibiting cardiotoxicity related to hERG inhibition in vivo. It is important to note, however that not all compounds which inhibit hERG activity in vitro will proceed to cause cardiotoxicity in vivo.
Where are hERG channels?
hERG is expressed in multiple tissues and cell types, including neural1, smooth muscle8 and tumour cells9,10. In the central nervous system of mammals, two other ERG channel genes are expressed (ERG2 and ERG3)11, and here heteromultimeric channel complexes of all three subunits can be formed12.
What is the hERG assay?
What is a 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. How does the hERG assay support cardiac studies? hERG activity manifests as the movement of potassium ions through a pore present in the hERG channel protein.
What is a hERG study?
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.
How did hERG get its name?
The funny name HERG, or written out ‘human ether-a-go-go related gene’, is derived from the similarity between this gene and the EAG (‘ether-a-go-go’) locus of the fruitfly Drosophila melanogaster.
What is a hERG assay?
Do you want a low or high IC50?
3 Fitting the Inhibitory Concentration (IC50) Curves The IC50 value is correlated with drug potency, i.e. the amount of drug necessary to produce the effect—the lower the IC50 value the more potent the drug [33].
What IC50 is considered toxic?
In these experimental conditions, the IC50 values allowed the substances to be arbitrarily ranked in three levels of toxicity: high toxicity, IC50 values < 0.1 mM; mild toxicity, 0.1 mM < IC50 values < 10 mM and low toxicity, IC50 values > 10 mM.
What is a good IC50?
In most cases, the IC50 of the best candidate compound should be lower to 10 micromolar, acceptable for NIH to screen the NCI60 program. In addition, the drug design should think over the related problem about the absorption, distribution, metabolism and excretion in our body.
What does an IC50 value tell you?
Abstract. Half-maximal inhibitory concentration (IC50) is the most widely used and informative measure of a drug’s efficacy. It indicates how much drug is needed to inhibit a biological process by half, thus providing a measure of potency of an antagonist drug in pharmacological research.
Is a high or low IC50 good?
The IC50 value is correlated with drug potency, i.e. the amount of drug necessary to produce the effect—the lower the IC50 value the more potent the drug [33].
Is a high IC50 good?
IC50 is the dose of the substance which inhibits the proliferation of half of the cells. It does not necessarily need to kill the cells. If you find high IC50, this means that the cell line is more resistant to drug1 than drug 2.
Is a low or high IC50 good?