BAY-549

BAY-549 (Azaindole 1) is an orally active and ATP-competitive ROCK inhibitor with IC₅₀s of 0.6 and 1.1 nM for human ROCK-1 and ROCK-2, respectively^[1]. IC50 & Target:IC50: 0.6 nM (Human ROCK-1), 1.1 nM (Human ROCK-2), 2.4 nM (Murine ROCK-2), 0.8 nM (Rat ROCK-2)^[1] In Vitro:BAY-549 (Azaindole 1) is a highly potent inhibitor of human ROCK-1 and ROCK-2, with IC₅₀s of 0.6 and 1.1 nM, respectively, and also inhibits murine ROCK-2 or rat ROCK-2 with IC₅₀s of 2.4 and 0.8 nM, respectively. BAY-549 also inhibits receptor tyrosine kinases TRK and FLT3, with IC₅₀s of 252 and 303 nM, respectively, but shows slight inhibition of MLCK and ZIP-kinase with IC₅₀s of 7.4 μM and 4.1 μM, respectively. BAY-549 induces vasorelaxation in vitro, and suppresses the phenylephrine-induced contraction of rabbit saphenous artery in a concentration dependent manner with an IC₅₀ value of 65 nM^[1]. In Vivo:BAY-549 (Azaindole 1) (0.03, 0.1, 0.3 mg/kg, i.v.) results in a dose-dependent and long-lasting decrease in blood pressure in anaesthetized normotensive rats. BAY-549 (3 and 10 mg/kg, p.o.) decreases blood pressure dose-dependently and persistently both in normotensive and hypertensive rats, and shows such effects even at 1 mg/kg in hypertensive rats. BAY-549 (0.1 and 0.3 mg/kg, i.v. bolus injections) causes decreased mean arterial blood pressure in a dose-related manner and only leads to a moderate and dose-independent increase in heart rate of anaesthetized dogs^[1].