Fasudil (HA-1077) hydrochloride

Fasudil hydrochloride (HA-1077; AT-877) is a potent inhibitor of ROCK-II, PKA, PKG, PKC, and MLCK with Ki of 0.33 μM, 1.6 μM, 1.6 μM, 3.3 μM and 36 μM, respectively. (In Vitro) :Fasudil Hydrochloride (100 μM) inhibits cell spreading, the formation of stress fibers, and expression of α-SMA with concomitant suppression of cell growth in rat HSCs (hepatic stellate cells) and human HSC-derived TWNT-4 cells.Fasudil Hydrochloride (50-100 μM; 24 hours) inhibits the LPA (lysophoaphatidic acid) -induced phosphorylation of ERK1/2, JNK, and p38 detected by western blotting in rat HSCs and human HSC-derived TWNT-4 cells.Fasudil Hydrochloride (25-100 μM; 24 hours) suppresses transcription of collagen and TIMP, stimulates transcription of MMP-1 in human HSC-derived TWNT-4 cells. (In Vivo) :Fasudil Hydrochloride (10 mg/kg; i.v.; 1 h before operation) exhibits protectable effects on cardiovascular disease and reduces the activation of JNK and attenuates mitochondrial-nuclear translocation of AIF under ischemic injury.Fasudil Hydrochloride (50 mg/kg/d; i.p.) inhibits acute and relapsing EAE (experimental autoimmune encephalomyelitis) induced by proteolipid protein PLP p139-151, reduces lymphocytes proliferation, results downregulation of interleukin (IL) -17 and a marked decrease of the IFN-γ/IL-4 ratio.Fasudil Hydrochloride (100 mg/kg/d; p.o.) significantly reduces incidence and pathological examination score of EAE (experimental autoimmune encephalomyelitis) in SJL/J mice, decreases inflammation, demyelination, axonal loss and APP positivein spinal cord in mice.