HA-1077 hydrochloride

HA-1077 hydrochloride用途

Fasudil(HA-1077；AT877)二盐酸盐是一种非特异性RhoA/ROCK抑制剂,对蛋白激酶也有抑制作用,其中ROCK1的Ki为0.33μM,ROCK2的IC50s为0.158μM和4.58μM、12.30μM和1.650μM,PKA、PKC、PKG的Ki分别为0.33和0.158μM。盐酸法舒地尔也是一种有效的钙离子通道拮抗剂和血管扩张剂[1][2][3]。

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HA-1077 hydrochloride名称

[ CAS 号 ]:
203911-27-7

[ 中文名 ]:
盐酸法舒地尔

[ 英文名 ]:
HA-1077 (hydrochloride)

[英文别名 ]:

HA-1077 (hydrochloride)
Fasudil dihydrochloride
HA-1077 dihydrochloride

HA-1077 hydrochloride生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> 钙通道

信号通路 >> 表观遗传学 >> PKC

研究领域 >> 癌症

信号通路 >> 抗感染 >> HIV

信号通路 >> 蛋白酪氨酸激酶 >> PKA

信号通路 >> 干细胞及 Wnt 通路 >> PKA

信号通路 >> 细胞周期/DNA损伤 >> 岩石

信号通路 >> 自噬 >> 自噬

信号通路 >> 干细胞及 Wnt 通路 >> 岩石

信号通路 >> TGF-beta/Smad 信号通路 >> PKC

信号通路 >> TGF-beta/Smad 信号通路 >> 岩石

[ 靶点 ]

PKA:4.58 μM (IC50)

PKC:12.3 μM (IC50)

p160ROCK:0.33 μM (Ki)

ROCK2:0.158 μM (IC50)

PKG:1.65 μM (IC50)

[体外研究]

二氢法舒地尔(100μM)抑制大鼠HSC(肝星状细胞)和人HSC衍生TWNT-4细胞中的细胞扩散、应力纤维的形成和α-SMA的表达,同时抑制细胞生长[4]。二氢法舒地尔(50-100μM；24小时)抑制LPA(溶血磷脂酸)诱导的大鼠HSC和人HSC衍生TWNT-4细胞中ERK1/2、JNK和p38的磷酸化[4]。二氢法舒地尔(25-100μM；24小时)抑制胶原蛋白和TIMP的转录,刺激人HSC衍生的TWNT-4细胞中MMP-1的转录[4]。Western Blot分析[4]细胞系：大鼠HSC和人HSC衍生的TWNT-4细胞浓度：50μM；100μM孵育时间：24小时结果：分别抑制LPA诱导的ERK1/2、JNK和p38 MAPK磷酸化60%、70%和90%。RT-PCR[4]细胞系：大鼠HSC和人HSC衍生的TWNT-4细胞浓度：25μM；50微米；100μM培养时间：24小时结果：I型胶原、a-SMA和TIMP-1的表达降低。

[体内研究]

二氢法舒地尔(10 mg/kg；静脉注射；术前1小时)对心血管疾病具有保护作用,可减少缺血损伤下JNK的活化,并减弱AIF线粒体核移位[5]。二氢法舒地尔(50 mg/kg/d；i.p.)抑制蛋白脂质蛋白PLP p139-151诱导的急性和复发性EAE(实验性自身免疫性脑脊髓炎),减少淋巴细胞增殖,导致白细胞介素(IL)-17下调,IFN-γ/IL-4比值显著降低[6]。二氢法舒地尔(100 mg/kg/d；p.o.)可显著降低SJL/J小鼠EAE(实验性自身免疫性脑脊髓炎)的发病率和病理检查分数,降低小鼠的炎症、脱髓鞘、轴突丢失和APP阳性脊髓[6]。动物模型：大鼠心肌缺血再灌注(250-300 g)[5]剂量：10 mg/kg给药：静脉注射；结果：Rho激酶、JNK被激活,AIF转位至细胞核。抑制Rho激酶活性,减少心肌梗死面积和心肌细胞凋亡。

[参考文献]

[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.

HA-1077 hydrochloride物理化学性质

[ 分子式 ]:
C₁₄H₂₁Cl₂N₃O₃S

[ 分子量 ]:
382.306

[ 精确质量 ]:
381.068054

[ PSA ]:
79.91000

[ LogP ]:
4.10600

[ 储存条件 ]:
-20°C，密闭，干燥

HA-1077 hydrochlorideMSDS

详细MSDS(安全技术说明书)

HA-1077 hydrochloride安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危险品运输编码 ]:
NONH for all modes of transport

[ RTECS号 ]:
HM4031166

[ 海关编码 ]:
2942000000

HA-1077 hydrochloride海关

[ 海关编码 ]: 2942000000

HA-1077 hydrochloride文献

Vasodilator actions of HA1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase.

Br. J. Pharmacol. 98 , 1091, (1989)

The in vitro and in vivo vasorelaxant effects of HA1077, 1-(5-isoquinolinesulphonyl)-homopiperazine HCl, a novel vasodilator were examined. The inhibitory effects of HA1077 on contractile responses to...

A new type of vasodilator, HA1077, an isoquinoline derivative, inhibits proliferation of bovine vascular smooth muscle cells in culture.

J. Pharmacol. Exp. Ther. 259 , 738, (1991)

The effects of a newly developed vasodilator agent, HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride], were investigated on the proliferation of cultured bovine aortic vascular smooth m...

Effects of HA1077, a protein kinase inhibitor, on myosin phosphorylation and tension in smooth muscle.

Eur. J. Pharmacol. 195 , 267, (1991)

We examined the effects of HA1077, a potent inhibitor of protein kinases in vitro, on the relationship between tension and myosin-light chain (MLC20) phosphorylation in the initial phase of contractio...

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