A diphenolurea compound that selectively activates human ether-a-go-go-related gene (hERG) K+-channel (EC50=10.5uM). Shown to significantly increase both steady-state and peak tail currents of hERG channels, but exhibits only a trivial effect on Kv4.3 and Kv1.5 channels. Causes a significant reduction in action potential duration (APD90) in patch clamp assays in Xenopus oocytes, HEK293 cells, and guinea pig cardiamyocyes that can be reversed by the addition of E-4031, a specific blocker of hERG channels. Also shown to activate IKr channel in cardiomyocytes and increase post-repolarization refractory time thereby alleviating hyper-excitability and producing antiarrhythmic effects. It can also restore IKr reduced by down-regulation of IKr expression.
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. Reconstituted product is stable for 6 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
