1-(5-Isoquinolinylsulfonyl)homopiperazine dihydrochloride, Fasudil dihydrochloride Chemical Properties

Density 

1.289

RTECS 

HM4031166

Flash point:

260℃

storage temp. 

Store at -20°C

solubility 

H2O: >10mg/mL

form 

solid

color 

white to off-white

Water Solubility 

Soluble in water and dimethylsulfoxide.

Safety Information

Safety Statements 

24/25

WGK Germany 

3

HS Code 

29339900

1-(5-Isoquinolinylsulfonyl)homopiperazine dihydrochloride, Fasudil dihydrochloride Usage And Synthesis

Description

Rho-associated kinase (ROCK), an effector of the small GTP-binding protein Rho, plays an important role in various cellular functions including vascular smooth muscle contraction, proliferation, and migration as well as inflammatory cell mobility. HA-1077 is a potent inhibitor of ROCK2 and additionally inhibits protein kinase c-related kinase 2 (PRK2), mitogen- and stress-activated protein kinase (MSK1), and mitogen activated protein kinase-activated protein kinase 1b (MAPKAP-K1b) with IC₅₀ values of 1.9, 4, 5, and 15 μM, respectively. By inhibiting the activity of ROCK, HA-1077 has been shown to reduce blood vessel constriction, decrease pulmonary arterial pressure, inhibit tumor angiogenesis, and improve insulin signaling in various rodent models. While originally marketed for the prevention of cerebral vasospasm in patients with subarachnoid hemorrhage, oral formulations of HA-1077 are used for the treatment of a wide range of cardiovascular diseases including pulmonary arterial hypertension and stable angina.

Chemical Properties

White fine crystalline powder

Uses

Fasudil dihydrochloride is used in the inhibition of contractile responses to potassium chloride, phenylephnne (PHE), prostaglandin and hepatic stellate cells spreading. It is also used in the formation of stress fibers and in medicine.

Uses

HA-1077 dihydrochloride has been used:

• to relax cantilevers
• in the functional assessment of isolated coronary arteries
• to investigate the effect of azaindole-1, fasudil on acute hypoxic pulmonary vasoconstriction (HPV)

Biochem/physiol Actions

Novel vasodilator agent which inhibits vascular smooth muscle contraction by acting as an intracellular Ca2+ antagonist.

in vivo

IC 50

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

References

[1] SHUNSUKE TAWARA  Hiroaki S. Progress of the study of rho-kinase and future perspective of the inhibitor.[J]. Yakugaku zasshi?: Journal of the Pharmaceutical Society of Japan, 2007, 127 3: 501-514. DOI: 10.1248/yakushi.127.501
[2] S. DAVIES. Specificity and mechanism of action of some commonly used protein kinase inhibitors.[J]. The Ukrainian Biochemical Journal, 2000, 24 1: 95-105. DOI: 10.1042/bj3510095
[3] MASAHIKO OKA. Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats.[J]. Circulation research, 2007, 100 6: 923-929. DOI: 10.1161/01.res.0000261658.12024.18
[4] LIMEI YIN. Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo.[J]. Molecular Cancer Therapeutics, 2007, 6 5: 1517-1525. DOI: 10.1158/1535-7163.mct-06-0689
[5] YUICHI KIKUCHI. A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats.[J]. Journal of Endocrinology, 2007, 192 3: 595-603. DOI: 10.1677/joe-06-0045

1-(5-Isoquinolinylsulfonyl)homopiperazine dihydrochloride, Fasudil dihydrochloride(203911-27-7)Related Product Information

• Homopiperazine
• FASUDIL