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Fasudil (HA-1077) HCl

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Catalog No.
A5734
蛋白激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
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200mg
¥ 700.00
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500mg
¥ 1,200.00
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Background

Fasudil (HA-1077) HCl is a selective inhibitor of ROCK with IC50 value of 0.74 μM [1].

Rho-associated protein kinase (ROCK) belongs to the AGC family of serine-threonine kinases and plays a pivotal role in regulating a variety of cellular processes. It has been reported that abnormal expression of ROCK is correlated with numerous diseases and infections [2].

Fasudil (HA-1077) HCl is a potent ROCK inhibitor and has a different structure with the reported ROCK inhibitor Y-27632. When tested with 2 human bladder cancer cell lines (5637 and UM-UC-3), Fasudil (HA-1077) HCl treatment inhibits cell proliferation, decreases cell migration and induced cell apoptosis in a dose dependent manner via blocking Rho/ROCK pathway [3]. In oral squmous cell carcinoma SCC-4 cells, administration of Fasudil (HA-1077) HCl markedly decreases cell motility and inhibits cell migration or invasion in a dose dependent manner (1, 50 and 100 μmol/L [4].

In the Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders, oral administration of Fasudil (HA-1077) HCl (100 mg/kg, daily) markedly increases the total white cell and monocyte numbers while prolonged survival time has trend but no statistical difference compared with the control group [2].

References:
[1].  Wickman, G., C. Lan, and B. Vollrath, Functional roles of the rho/rho kinase pathway and protein kinase C in the regulation of cerebrovascular constriction mediated by hemoglobin: relevance to subarachnoid hemorrhage and vasospasm. Circ Res, 2003. 92(7): p. 809-16.
[2].  William, B.M., et al., Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders. Hematology, 2015.
[3].  Abe, H., et al., The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer, 2014. 14: p. 412.
[4].   Moreira Carboni, S.S., et al., HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma. Anticancer Drugs, 2015.

文献引用

1. Deng X, Ji Z, et al. "Suppressing the Na(+)/H(+) exchanger 1: a new sight to treat depression." Cell Death Dis. 2019 May 8;10(5):370. PMID:31068571
2. Hu, Haiyan, et al. "Fasudil prevents calcium oxalate crystal deposit and renal fibrogenesis in glycoxylate-induced nephrolithic mice." Experimental and Molecular Pathology (2015). PMID:25697583

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt327.83
Cas No.105628-07-7
FormulaC14H17N3O2S.HCl
Solubility≥16.4mg/mL in DMSO, ≥4.81 mg/mL in EtOH with ultrasonic, ≥50 mg/mL in H2O
Chemical Name5-(1,4-diazepan-1-ylsulfonyl)isoquinoline;hydrochloride
SDFDownload SDF
Canonical SMILESC1CNCCN(C1)S(=O)(=O)C2=CC=CC3=C2C=CN=C3.Cl
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

5637, UM-UC-3 以及 SCC-4细胞系

溶解方法

在DMSO中的溶解度> 16.4 mg/ml。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0~30μM

应用

Lysophosphatidic acid和geranylgeraniol可以引起细胞增殖和迁移的增加,该效应与RhoA活性的升高以及ROCK表达的上调有关。Fasudil(HA-1077)可以有效地抑制细胞增殖和迁移,并以剂量依赖的方式诱导细胞凋亡。 此外,Fasudil(HA-1077)也可以显著抑制ROCK-I和ROCK-II的表达,但不影响RhoA活性。

动物实验 [2]:

动物模型

Cbl/Cbl-b缺陷驱动的鼠骨髓增生性疾病模型

剂量

100 mg/kg /天,口服

应用

在Cbl/Cbl-b缺陷驱动的鼠骨髓增生性疾病模型中,通过2周的治疗,用fasudil治疗的小鼠中,总白细胞和单核细胞计数显著降低。 同时,还观察到fasudil治疗小鼠存活率提高的趋势,但并未达到统计学差异。 值得注意的是,在两个fasudil治疗的小鼠中,研究观察到超过27周的长期存活率,两倍于Cbl / Cbl-b DKO MPD模型中16周平均寿命。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Abe, H., et al., The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer, 2014. 14: p. 412.

[2] William, B.M., et al., Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders. Hematology, 2015.

质量控制

化学结构

Fasudil (HA-1077) HCl

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Fasudil (HA-1077) HCl

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