Recent developments in computational prediction of HERG blockage.

TitleRecent developments in computational prediction of HERG blockage.
Publication TypeJournal Article
Year of Publication2013
AuthorsWang S, Li Y, Xu L, Li D, Hou T
JournalCurrent topics in medicinal chemistry
Volume13
Issue11
Pagination1317-26
Date Published2013
Abstract

The blockage of the voltage dependent ion channel encoded by human ether-a-go-go related gene (hERG) may lead to drug-induced QT interval prolongation, which is a critical side-effect of non-cardiovasular therapeutic agents. Therefore, identification of potential hERG channel blockers at the early stage of drug discovery process will decrease the risk of cardiotoxicity-related attritions in the later and more expensive development stage. Computational approaches provide economic and efficient ways to evaluate the hERG liability for large-scale compound libraries. In this review, the structure of the hERG channel is briefly outlined first. Then, the latest developments in the computational predictions of hERG channel blockers and the theoretical studies on modeling hERG-blocker interactions are summarized. Finally, the challenges of developing reliable prediction models of hERG blockers, as well as the strategies for surmounting these challenges, are discussed.

DOI10.1093/jxb/ert290
Alternate JournalCurr Top Med Chem