Fasudil dihydrochloride, also known as HA-1077 and AT877, is a nonspecific inhibitor of RhoA/ROCK. It exhibits inhibitory effects on protein kinases, including ROCK1 with a Ki value of 0.33 μM, as well as ROCK2, PKA, PKC, and PKG with IC 50 values of 0.158 μM, 4.58 μM, 12.30 μM, and 1.650 μM, respectively. Additionally, Fasudil dihydrochloride demonstrates potent Ca 2+ channel blocking activity and acts as a vasodilator [1] [2] [3].

Fasudil dihydrochloride, at concentrations of 100 μM, effectively inhibits cell spreading, stress fiber formation, and α-SMA expression, leading to the suppression of cell proliferation in both rat and human hepatic stellate cells (HSCs), including TWNT-4 cells derived from human HSCs. At concentrations ranging from 50 to 100 μM over 24 hours, fasudil dihydrochloride also prevents lysophosphatidic acid (LPA)-stimulated phosphorylation of ERK1/2, JNK, and p38, as evidenced by western blot analyses in these cell types. Moreover, at doses between 25 to 100 μM and over a 24-hour exposure, this compound diminishes collagen and TIMP transcription, while enhancing MMP-1 transcription in human HSC-derived TWNT-4 cells. Detailed western blot analysis revealed a significant inhibition of LPA-induced phosphorylation of ERK1/2, JNK, and p38 MAPK by 60%, 70%, and 90%, respectively, in rat and human HSC-derived TWNT-4 cells at 50 and 100 μM. RT-PCR data further confirmed a reduction in the expression of type I collagen, α-SMA, and TIMP-1 under the influence of fasudil dihydrochloride at concentrations of 25, 50, and 100 μM after 24 hours.

Administered intravenously at a dosage of 10 mg/kg one hour before surgery, Fasudil dihydrochloride demonstrates protective effects against cardiovascular diseases by reducing JNK activation and mitigating the mitochondrial-nuclear translocation of AIF following ischemic damage. Furthermore, at a daily intraperitoneal dose of 50 mg/kg, it effectively impedes both acute and relapsing experimental autoimmune encephalomyelitis (EAE) induced by the proteolipid protein PLP p139-151, curtails lymphocyte proliferation, downregulates interleukin (IL)-17, and significantly lowers the IFN-γ/IL-4 ratio. At an oral dose of 100 mg/kg/day, Fasudil dihydrochloride markedly decreases the occurrence and pathological severity of EAE in SJL/J mice, reducing inflammation, demyelination, axonal loss, and APP positivity in the spinal cord. This compound's administration in a myocardial ischemia and reperfusion animal model in rats (250-300 g) demonstrated its ability to inhibit Rho-kinase activity, which in turn lessened myocardial infarct size and prevented cardiac cell apoptosis.