Modulation of K_v 11.1 (hERG) channels by 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), a novel small molecule activator.

ABSTRACT:

Background and purpose

Activators of K_v 11.1 (hERG) channels have potential utility in the treatment of acquired and congenital long QT (LQT) syndrome. Here, we describe a new hERG channel activator, 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), with a chemical structure distinct from previously reported compounds.

Experimental approach

Conventional electrophysiological methods were used to assess the effects of ITP-2 on hERG1a and hERG1a/1b channels expressed heterologously in HEK-293 cells.

Key results

ITP-2 selectively increased test pulse currents (EC₅₀ 1.0 μM) and decreased tail currents. ITP-2 activated hERG1a homomeric channels primarily by causing large depolarizing shifts in the midpoint of vol

SUBMITTER: Sale H 

PROVIDER: S-EPMC5513870 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature