Fasudil (HA-1077) HCl
(Synonyms: 盐酸法舒地尔; HA-1077 Hydrochloride; AT-877 Hydrochloride) 目录号 : GC14289Fasudil (HA-1077; AT877) Hydrochloride 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 μ ;M, 1.650 μM 分别代表 ROCK2 和 PKA、PKC、PKG。 Fasudil (HA-1077) HCl 也是一种有效的 Ca2+ 通道拮抗剂和血管扩张剂。
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
5637, UM-UC-3 and SCC-4 cell lines |
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Preparation method |
The solubility of this compound in DMSO is >16.4 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0-30 μM |
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Applications |
Lysophosphatidic acid and geranylgeraniol induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. Fasudil (HA-1077) could suppress cell proliferation and migration, and also induce apoptosis in a dose-dependent manner. Fasudil (HA-1077) also dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. |
| Animal experiment [2]: | |
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Animal models |
Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders |
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Dosage form |
100 mg/kg daily by oral gavage |
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Application |
In the Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders, by 2 weeks of treatment, total white cell and monocyte counts were significantly lower in mice treated with fasudil. A trend towards improved survival in fasudil-treated mice that did not reach statistical significance was also observed. Notably, prolonged survival beyond 27 weeks was seen in two fasudil-treated mice, nearly twice the 16-week average life-span in the Cbl/Cbl-b DKO MPD model. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. |
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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.
| Cas No. | 105628-07-7 | SDF | |
| 别名 | 盐酸法舒地尔; HA-1077 Hydrochloride; AT-877 Hydrochloride | ||
| 化学名 | 5-(1,4-diazepan-1-ylsulfonyl)isoquinoline;hydrochloride | ||
| Canonical SMILES | C1CNCCN(C1)S(=O)(=O)C2=CC=CC3=C2C=CN=C3.Cl | ||
| 分子式 | C14H17N3O2S.HCl | 分子量 | 327.83 |
| 溶解度 | ≥ 16.4mg/mL in DMSO, ≥ 4.81 mg/mL in EtOH with ultrasonic, ≥ 50 mg/mL in Water | 储存条件 | Store at 4°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0504 mL | 15.2518 mL | 30.5036 mL |
| 5 mM | 0.6101 mL | 3.0504 mL | 6.1007 mL |
| 10 mM | 0.305 mL | 1.5252 mL | 3.0504 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。