ROCK-IN-2 (Azaindole 1) is a selective and ATP-competitive ROCK inhibitor with IC50 of 0.6 and 1.1 nM for human ROCK-1 and ROCK-2.

ROCK1:0.6 nM (cell free), ROCK2:1.1 nM (cell free)

Azaindole 1 a highly potent inhibitor of human ROCK-1 and ROCK-2 (IC50s: 0.6 and 1.1?nM) and also inhibits murine ROCK-2 or rat ROCK-2 (IC50s: 2.4 and 0.8?nM). Azaindole 1 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. Azaindole 1 induces vasorelaxation in vitro and suppresses the phenylephrine-induced contraction of the rabbit saphenous artery in a concentration-dependent manner (IC50: 65?nM).

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. Azaindole 1 (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. Azaindole 1 (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 anesthetized dogs.

Male Wistar rats (300-350?g) are anesthetized with thiopental 100?mg/kg intraperitoneally (i.p.). A tracheotomy is performed and catheters are inserted into the femoral artery for blood pressure and heart rate measurements and into the femoral vein for test drug administration. The animals are ventilated with room air and their body temperature is controlled. Azaindole 1 is administered intravenously (i.v.) in doses of 0.03-0.1?mg/kg. The vehicle Transcutol/Cremophor EL/physiological saline (19/10/80 = v/v/v) without test drug is used as control. The volume administered is 1?mL/kg. Six animals are treated per group.