Figure 1.

ROCK1 versus ROCK2 selectivity, in vitro. (A) KD025 selectively inhibited ROCK2 over ROCK1, whereas isoform-nonselective Y27632 inhibited ROCK1 and ROCK2 to a similar extent in a recombinant enzyme system with truncated catalytic domains. IC₅₀ values for each drug are indicated on the graphs. (B) ROCK2 inhibition by KD025 was competitive with ATP. (C) Systemic administration of KD025 (200 mg/kg via oral gavage 1 h before harvesting the tissues) inhibited ROCK activity in the brain, as well as in the heart, as measured by MYPT1 phosphorylation in mice (n = 2 each vehicle and KD025). Total MYPT1 levels did not show a consistent change. The effect was comparable to that of isoform non-selective ROCK inhibitor hydroxyfasudil (HF, 10 mg/kg, intraperitoneal).