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Fasudil Hydrochloride Hydrate

Product NameFasudil Hydrochloride Hydrate
CAS186694-02-0
MFC14H20ClN3O3S
MW345.84
EINECS
MOL File186694-02-0.mol

Usage And Synthesis

Uses

Fasudil (HA-1077; AT877) hydrochloride semihydrate is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an Ki of 0.33 μM for ROCK1, IC50s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil hydrochloride semihydrate is also a potent Ca2+ channel antagonist and vasodilator[1][2][3].

Definition

ChEBI: Fasudil hydrochloride hydrate is a hydrate that is the hemihydrate form of fasudil hydrochloride. It is a drug indicated for the prevention of cerebral vasospasm and ensuing cerebral ischemia following surgery for subarachnoid hemorrhage. It has a role as an antihypertensive agent, a calcium channel blocker, an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, a neuroprotective agent, a nootropic agent and a vasodilator agent. It contains a fasudil hydrochloride.

in vivo

Fasudil hydrochloride semihydrate (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^[5]. Fasudil hydrochloride semihydrate (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^[6]. Fasudil hydrochloride semihydrate (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^[6].

Animal Model:	Myocardial ischemia and reperfusion in rat (250-300 g)^[5]
Dosage:	10 mg/kg
Administration:	Intravenous injection; 1 h before operation
Result:	Activated the Rho-kinase, JNK, and resulted AIF translocated to the nucleus. Inhibited Rho-kinase activity, and reduced myocardial infarct size and heart cell apoptosis.

IC 50

PKA: 4.58 μM (IC₅₀); p160ROCK: 0.33 μM (Ki); ROCK2: 0.158 μM (IC₅₀); PKC: 12.3 μM (IC₅₀); PKG: 1.65 μM (IC₅₀)

References

[1] Chen M, et al. Fasudil and its analogs: a new powerful weapon in the long war against central nervous system disorders Expert Opin Investig Drugs. 2013 Apr;22(4):537-50. DOI:10.1517/13543784.2013.778242
[2] Huang XN, et al. The effects of fasudil on the permeability of the rat blood-brain barrier and blood-spinal cordbarrier following experimental autoimmune encephalomyelitis. J Neuroimmunol. 2011 Oct 28;239(1-2):61-7. DOI:10.1016/j.jneuroim.2011.08.015
[3] Uehata M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997 Oct 30;389(6654):990-4. DOI:10.1038/40187
[4] Fukushima M, et al. Fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity in hepatic stellate cells. Liver Int. 2005 Aug;25(4):829-38. DOI:10.1111/j.1478-3231.2005.01142.x
[5] Zhang J, et al. Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIF translocation. Clin Chim Acta. 2009 Mar;401(1-2):76-80. DOI:10.1016/j.cca.2008.11.016
[6] Sun X, et al. The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2006 Nov;180(1-2):126-34. Epub 2006 Sep 22. DOI:10.1016/j.jneuroim.2006.06.027

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