Fasudil (HA-1077) is a potent inhibitor of ROCK1, PKA, PKC, and MLCK.

MLCK:55 μM(Ki), PKA:1.0 μM(Ki), PKC:9.3 μM(Ki), ROCK1:0.33 μM(Ki)

Fasudil（ hydrochloride ）通过占据ATP结合位点的腺苷口袋，具有血管扩张作用[1]。Fasudil属于一类钙通道拮抗剂，能够与Ca2+诱导的去极化兔主动脉收缩进行竞争性抑制。Fasudil能够抑制KCl、苯肾上腺素（PHE）和前列腺素（PG）F2a诱导的收缩反应[2]。此外，Fasudil通过抑制5-羟色胺、去甲肾上腺素、组胺、血管紧张素及多巴胺诱导的螺旋条收缩显示出血管扩张作用[3]。Fasudil诱导肌动蛋白应力纤维的紊乱及细胞迁移的抑制[4]，抑制肝星状细胞的扩散、应力纤维的形成以及α-SMA的表达，同时伴有细胞生长的抑制，但不诱导细胞凋亡。Fasudil抑制LPA诱导的ERK1/2、JNK和p38 MAPK的磷酸化[5]。

Fasudil (30 μg) 通过犬只冠状动脉内注射，可使脑血流量(CBF)约增加50%。Fasudil（0.01、0.03、0.1及0.3 mg/kg，推注，静脉给药）对于平均血压(MBP)的减少和心率(HR)、血管血流量(VBF)、脑血流量(CBF)、肾血流量(RBF)及前臂血流量(FBF)的增加具有剂量依赖性效应。Fasudil总剂量1.0 ng/mL可增加心输出量。Fasudil的静脉输注显著降低MBP，左室收缩压和总外周阻力，同时增加HR和心输出量，但并未显著改变右心房压、dP/dt或犬只左心室分钟功的变化。Fasudil的应用在心血管疾病中展现出保护作用，减少JNK激活，并在缺血损伤条件下减缓线粒体-核转移的AIF。Fasudil口服（100 mg/kg/天）显著降低了以PLP p139-151免疫的SJL/J小鼠的EAE发生率及平均最大临床评分。Fasudil处理抑制了小鼠脾细胞对抗原的增殖反应，口服Fasudil减少了处理小鼠脊髓中的炎症、脱髓鞘、轴突损失和APP阳性。

Cyclic AMP-dependent protein kinase activity is assayed in a reaction mixture containing, in a final volume of 0.2 mL, 50 mM Tris-HCl (pH 7.0), 10 mM magnesium acetate, 2 mM EGTA, 1 μM cyclic AMP or absence of cyclic AMP, 3.3 to 20 μM [r-32P] ATP (4×105 c.p.m.), 0.5 μg of the enzyme, 100 μg of histone H2B and compound. The mixture is incubated at 30°C for 5 min. The reaction is terminated by adding 1mL of ice-cold 20% trichloroacetic acid after adding 500 μg of bovine serum albumin as a carrier protein. The sample is centrifuged at 3000 r.p.m. for 15min, the pellet is resuspended in ice-cold 10% trichloro-acetic acid solution and the centrifugation-resuspension cycle is repeated three times. The final pellet is dissolved in 1 mL of 1 N NaOH and radioactivity is measured with a liquid scintillation counter[1].