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.

Is low IC50 good?

Low IC50 value means that the drug is effective at low concentrations, and thus will show lower systemic toxicity when administered to the patient.

What is the Cheng Prusoff equation?

The Cheng-Prusoff equation defines the theoretical relation- ship between the measured IC50 for a competitive inhibitor of given Ki, the concentration of labeled ligand, and the KD of the ligand-receptor interaction.

What is hERG receptor?

hERG (the human Ether-à-go-go-Related Gene) is a gene (KCNH2) that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel.

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.

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.

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’s a good IC50 value?

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 is the NCBI ID for thioridazine?

National Center for Biotechnology Information (NCBI). PMID 28520378. Bookshelf ID: NBK424018. “Thioridazine”. Drug Information Portal.

What is the ICD 10 code for thioridazine?

PMID 28520378. Bookshelf ID: NBK424018. “Thioridazine”. Drug Information Portal. U.S. National Library of Medicine. Antipsychotic Mellaril Removed from Market Schizophrenia Daily News Blog.

Can the hERG ic50-c Max ratio be used to predict drug-induced TDP?

Purpose: To validate the use of the hERG IC50:C max ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. Data sources: Medline (between 1966 and March 2017) was accessed for hERG IC50 and C max values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP.

What is the mechanism of action of thioridazine?

Thioridazine is known to kill extensively drug-resistant tuberculosis and to make methicillin-resistant Staphylococcus aureus sensitive to β-lactam antibiotics. A possible mechanism of action for the drug’s antibiotic activity is via the inhibition of bacterial secretion pumps.