Improvement of cardiomyocyte function by a novel pyrimidine-based CaMKII-inhibitor.

ABSTRACT:

Objective

Pathologically increased activity of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and the associated Ca²⁺-leak from the sarcoplasmic reticulum are recognized to be important novel pharmacotherapeutic targets in heart failure and cardiac arrhythmias. However, CaMKII-inhibitory compounds for therapeutic use are still lacking. We now report on the cellular and molecular effects of a novel pyrimidine-based CaMKII inhibitor developed towards clinical use.

Methods and results

Our findings demonstrate that AS105 is a high-affinity ATP-competitive CaMKII-inhibitor that by its mode of action is also effective against autophosphorylated CaMKII (in contrast to the commonly used allosteric CaMKII-inhibitor KN-93). In isolated atrial cardiomyocytes

SUBMITTER: Neef S 

PROVIDER: S-EPMC5820112 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature