ITP-2 is a novel small molecule activator of Kv11.1 (hERG) channel (216% over control at 3 uM for hERG1a activation).
ITP-2 selectively increases test pulse currents (EC50=1.0 μM) and decreases tail currents, activates hERG1a homomeric channels primarily by causing large depolarizing shifts in the midpoint of voltage-dependent inactivation and hyperpolarizing shifts in the voltage-dependence of activation.
ITP-2 exerts agonistic effect from extracellular side of the membrane and could activate the arrhythmia-associated trafficking-deficient LQT2 mutant G601S with 2 fold reduced potency, may be potentially useful in the development of LQT2 therapeutics.
