186694-02-0

186694-02-0 structure

Name: Fasudil Hydrochloride Hydrate
Chemical Name: 5-(1,4-diazepan-1-ylsulfonyl)isoquinoline,hydrate,dihydrochloride
CAS Number: 186694-02-0
Molecular Formula: C₂₈H₃₈Cl₂N₆O₅S₂
Molecular Weight: 673.67500
Catalog: Signaling Pathways Anti-infection HIV
Create Date: 2016-11-25 03:39:54
Modify Date: 2024-01-10 10:20:45
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].

Name	5-(1,4-diazepan-1-ylsulfonyl)isoquinoline,hydrate,dihydrochloride
Synonyms	Fasudil hydrochloride hemihydrate Fasudil hydrochloride hydrate Eril-S UNII-LI4L0R5Y7T

Description	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].
Related Catalog	Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel Signaling Pathways >> Epigenetics >> PKC Research Areas >> Cancer Signaling Pathways >> Anti-infection >> HIV Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PKA Signaling Pathways >> Stem Cell/Wnt >> PKA Signaling Pathways >> Cell Cycle/DNA Damage >> ROCK Signaling Pathways >> Autophagy >> Autophagy Signaling Pathways >> Stem Cell/Wnt >> ROCK Signaling Pathways >> TGF-beta/Smad >> PKC Signaling Pathways >> TGF-beta/Smad >> ROCK
Target	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)
In Vitro	Fasudil hydrochloride semihydrate (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[4]. Fasudil hydrochloride semihydrate (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[4]. Fasudil hydrochloride semihydrate (25-100 μM; 24 hours) suppresses transcription of collagen and TIMP, stimulates transcription of MMP-1 in human HSC-derived TWNT-4 cells[4]. Western Blot Analysis[4] Cell Line: Rat HSCs and human HSC-derived TWNT-4 cells Concentration: 50 μM; 100 μM Incubation Time: 24 hours Result: Suppressed the LPA-induced phosphorylation of ERK1/2, JNK and p38 MAPK by 60%, 70%,and 90%, respectively. RT-PCR[4] Cell Line: Rat HSCs and human HSC-derived TWNT-4 cells Concentration: 25 μM; 50 μM; 100 μM Incubation Time: 24 hours Result: Reduced the expression of type I collagen, a-SMA, and TIMP-1.
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.
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. [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. [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. [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. [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. [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.

Molecular Formula	C₂₈H₃₈Cl₂N₆O₅S₂
Molecular Weight	673.67500
Exact Mass	672.17200
PSA	150.59000
LogP	6.67230

Hazard Codes	Xn

186694-02-0	105628-07-7
1808255-64-2	591229-40-2
206752-36-5	863406-85-3
145821-57-4	7081-40-5
60789-62-0	123333-71-1
2229282-33-9	1158522-08-7
940364-43-2	2742028-61-9
134104-43-1	131615-57-1
6906-52-1	930439-75-1
1018584-77-4	1375289-11-4