NAV

hERG inhibition (predictor II)


hERG, also known as ether-a-go-go related gene, encodes the potassium channel Kv11.1 and plays a key role in the generation of cardiac action potentials. Hence, inhibition of hERG channels is associated with QT prolongation and sudden cardiac death. Due to this important effect, it is of major importance to assess hERG blockage by compounds in early drug discovery. This inhibitory property can be predicted in silico by different drug descriptors such as log P and log S and using different modeling methods such as Estate Fingerprint, CDK Fingerprint and Substructure Fingerprint.1 The presence of different variables requires the use and comparison of different models and thus, in DrugBank we include two different hERG predictors called hERG inhibition (predictor I) and hERG inhibition (predictor II).

In the predicted ADMET features found in DrugBank, the hERG inhibition is studied using the prediction software admetSAR 2 and the terms found in the table on the drug card should be considered as follows:

Value - it can be presented by  "non-inhibitor", "weak inhibitor", or "inhibitor"
Probability - it presents a number between 0-1 and it indicates the certainty of the value describing the ADMET property of this drug based on the prediction software. 

For example, "There is a 84.03% probability that the drug X is an inhibitor of hERG based on the prediction of admetSAR software."

References:

  1. Zhang C, Zhou Y, Gu S, Wu Z, Wu W, Liu C, Wang K, Liu G, Li W, Lee PW, Tang Y: In silico prediction of hERG potassium channel blockage by chemical category approaches. Toxicol Res (Camb). 2016 Jan 14;5(2):570-582. doi: 10.1039/c5tx00294j. eCollection 2016 Mar 1. [PubMed:30090371]
  2. Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y: admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model. 2012 Nov 26;52(11):3099-105. doi: 10.1021/ci300367a. Epub 2012 Nov 1. [PubMed:23092397]