Removal of human ether-à-go-go related gene (hERG) K+ channel affinity through rigidity: a case of clofilium analogues

…, E Klaasse, J Brussee, AP IJzerman

Index: Carvalho, Joao F. S.; Louvel, Julien; Doornbos, Maarten L. J.; Klaasse, Elisabeth; Yu, Zhiyi; Brussee, Johannes; Ijzerman, Adriaan P. Journal of Medicinal Chemistry, 2013 , vol. 56, # 7 p. 2828 - 2840

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Citation Number: 7

Abstract

Cardiotoxicity is a side effect that plagues modern drug design and is very often due to the off-target blockade of the human ether-à-go-go related gene (hERG) potassium channel. To better understand the structural determinants of this blockade, we designed and synthesized a series of 40 derivatives of clofilium, a class III antiarrhythmic agent. These were evaluated in radioligand binding and patch-clamp assays to establish structure–affinity relationships ...