Referenced in: none

Automatically associated channels: Kv11.1

Title: A quantitative assessment of hERG liability as a function of lipophilicity.

Authors: Michael J Waring, Craig Johnstone

Journal, date & volume: Bioorg. Med. Chem. Lett., 2007 Mar 15 , 17, 1759-64

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17239590

Abstract
The impact of lipophilicity as a factor contributing to hERG potency is assessed for a large dataset of compounds of differing ionisation type. This dataset is derived from compounds tested in the IonWorks-based in vitro electrophysiology hERG assay at AstraZeneca. Using logistic regression, a quantification of the risk associated with increasing lipophilicity is presented. The anticipated differences between acidic, basic and neutral compounds are apparent in the data but lipophilicity is shown to be a stronger driver for hERG potency than might have been expected. Simple rules defining target lipophilicity values for minimizing hERG liability are derived.