A-484954

A-484954 is a highly selective eukaryotic elongationfactor-2 kinase(eEF2K) inhibitor, with an IC₅₀ of 280 nM. IC50 & Target:IC50: 280 nM (eEF2K)^[1]. In Vitro:A-484954 is a highly selective eEF2K inhibitor with an IC₅₀ value of 280 nM against eEF2K in the enzymatic assay and little activity against a wide panel of serine/threonine and tyrosine kinases. In enzymatic assay, the IC₅₀ value of A-484954 is increased as the concentration of ATP increased but unaffected by increasing concentrations of calmodulin^[1]. In Vivo:A484954 causes relaxation in E (+) and E (-) aorta or mesenteric artery precontracted with NA. Pretreatment with L-NAME but not indomethacin or cimetidine partially inhibits the A484954-induced relaxation in mesenteric artery^[2]. Long-term A-484954 treatment inhibits MCT-induced increases PA pressure. It is revealed that A-484954 inhibits MCT-induced PA hypertrophy and fibrosis but not impairment of endothelium-dependent and -independent relaxation. Furthermore, A-484954 inhibits MCT-induced NADPH oxidase-1 expression and ROS generation as well as matrix metalloproteinase-2 activation^[3].