Fasudil (HA-1077) HCl
(Synonyms: 盐酸法舒地尔; HA-1077 Hydrochloride; AT-877 Hydrochloride) 目录号 : GC14289
Fasudil（法舒地尔；HA-1077；AT877）是一种非特异性RhoA/ROCK抑制剂，对ROCK1的Ki为0.33μM，IC50为0.158μM，对ROCK2和PKA、PKC、PKG的IC50分别为4.58μM、12.30μM、1.650μM。
Cas No.:105628-07-7
Sample solution is provided at 25 µL, 10mM.
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Fasudil (HA-1077; AT877) is a non-specific RhoA/ROCK inhibitor with a Ki of 0.33μM and an IC50 of 0.158μM for ROCK1, and IC50 of 4.58μM, 12.30μM, and 1.650μM for ROCK2, PKA, PKC, and PKG, respectively[1]. The monomeric G protein RhoA and its activated target Rho kinase (ROCK) constitute the RhoA/ROCK signaling pathway, which has the function of inducing cytoskeletal reorganization, cell migration, and stress fiber formation, and also affects endothelial permeability, tissue compatibility, cell proliferation, and apoptosis[2, 3]. Fasudil is also an effective Ca2+ channel antagonist and vasodilator[4].
In vitro, Fasudil (0-30μM) treatment of human bladder cancer cell lines (5637 and UM-UC-3 cells) for 72h inhibited cell proliferation and migration in a dose-dependent manner, induced cell apoptosis, and significantly reduced the expression of ROCK-I and ROCK-II[5]. Fasudil (0.04, 0.2, 1μg/mL) pre-treated the co-culture system established by neutrophils and human pulmonary microvascular endothelial cells (HPMECs) for 30min, reduced neutrophil transendothelial cell migration, and inhibited neutrophil endothelial chemotaxis[6]. Fasudil (100μM) treatment of rat hepatic stellate cells and human hepatic stellate cell-derived TWNT-4 cells inhibited cell extension, stress fiber formation, and α-SMA expression, stimulated the production and transcription of matrix metalloproteinase-1 (MMP-1), and enhanced collagenase activity[7].
In vivo, Fasudil (10mg/kg) was intravenously administered to mice after myocardial ischemia/reperfusion injury, inhibiting c-Jun N-terminal kinase (JNK)-mediated apoptosis-inducing factor (AIF) translocation and reducing cardiomyocyte apoptosis during ischemia/reperfusion[8].
References:
[1] Chen M, Liu A, Ouyang Y, et al. Fasudil and its analogs: a new powerful weapon in the long war against central nervous system disorders?[J]. Expert opinion on investigational drugs, 2013, 22(4): 537-550.
[2] Crosas-Molist E, Samain R, Kohlhammer L, et al. Rho GTPase signaling in cancer progression and dissemination[J]. Physiological Reviews, 2022, 102(1): 455-510.
[3] Radeva M Y, Waschke J. Mind the gap: mechanisms regulating the endothelial barrier[J]. Acta physiologica, 2018, 222(1): e12860.
[4] Chen Y, Yuan T, Zhang H, et al. Fasudil evokes vasodilatation of rat mesenteric vascular bed via Ca2+ channels and Rho/ROCK pathway[J]. European journal of pharmacology, 2016, 788: 226-233.
[5] Abe H, Kamai T, Hayashi K, et al. The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells[J]. BMC cancer, 2014, 14: 1-12.
[6] Wang J, Xu J, Zhao X, et al. Fasudil inhibits neutrophil-endothelial cell interactions by regulating the expressions of GRP78 and BMPR2[J]. Experimental cell research, 2018, 365(1): 97-105.
[7] Fukushima M, Nakamuta M, Kohjima M, et al. Fasudil hydrochloride hydrate, a Rho‐kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity in hepatic stellate cells[J]. Liver international, 2005, 25(4): 829-838.
[8] Zhang J, Li X X, Bian H J, et al. Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIF translocation[J]. Clinica Chimica Acta, 2009, 401(1-2): 76-80.
Fasudil（法舒地尔；HA-1077；AT877）是一种非特异性RhoA/ROCK抑制剂，对ROCK1的Ki为0.33μM，IC50为0.158μM，对ROCK2和PKA、PKC、PKG的IC50分别为4.58μM、12.30μM、1.650μM[1]。单体G蛋白RhoA及其激活靶点Rho激酶（ROCK）组成了RhoA/ROCK信号通路，该通路具有诱导细胞骨架重组、细胞迁移和应力纤维形成功能，还影响内皮通透性、组织相容性、细胞增殖、细胞凋亡等[2, 3]。Fasudil也是一种有效的Ca2+通道拮抗剂和血管扩张剂[4]。
在体外，Fasudil（0-30μM）处理人膀胱癌细胞系（5637和UM-UC-3细胞）72h，均以剂量依赖性方式抑制了细胞增殖和迁移，诱导了细胞凋亡，显著降低了ROCK-I和ROCK-II的表达[5]。Fasudil（0.04、0.2、1μg/mL）预处理中性粒细胞和人肺微血管内皮细胞（HPMECs）建立的共培养系统30min，减少了中性粒细胞跨内皮细胞迁移，抑制了中性粒细胞内皮趋化性[6]。Fasudil（100μM）处理大鼠肝星状细胞和人肝星状细胞来源的TWNT-4细胞，抑制了细胞伸展、应力纤维的形成和α-SMA的表达，刺激基质金属蛋白酶-1（MMP-1）的产生和转录，并增强胶原酶活性[7]。
在体内，Fasudil（10mg/kg）通过静脉注射治疗心脏缺血/再灌注损伤后的小鼠，抑制了c-Jun氨基末端激酶（JNK）介导的凋亡诱导因子（AIF）转位，减少了缺血再灌注时心肌细胞凋亡[8]。
| Cell experiment [1]: | |
Cell lines | 5637 cells、UM-UC-3 cells |
Preparation Method | 5637 cells and UM-UC-3 cells (5×104/well) were seeded into 96-well plates in serum-containing medium and were allowed to attach for 24h. Then the medium was removed and replaced with new medium containing 0, 1, 10, 30μM of Fasudil. After being cultured for 72h, the cells were incubated with 50μL of MTT(5mg/mL) for 1h. The formazan product was dissolved in 100 mL of DMSO and its absorbance was measured at a wavelength of 630nm in a microplate reader. Proliferation of 5637 cells and UM-UC-3 cells was also assessed by quantitative ELISA. |
Reaction Conditions | 0, 1, 10, 30μM; 72h |
Applications | Fasudil inhibits the proliferation of 5637 cells and UM-UC-3 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female Wistar rats |
Preparation Method | Five experimental groups were studied. 1.sham operation. (n=30); 2.left anterior descending branch(LAD) was occluded for 30 min and reperfused for 180min plus administration of normal saline(NS)[1ml normal saline i.v. 1h before operation] (n=18); 3.LAD was occluded for 30min and reperfused for 180min plus administration of Fasudil, inhibitor of Rho-kinase[10mg/kg i.v. 1h before operation. Fasudil was dissolved in 1ml normal saline] (n=18); 4.LAD was occluded for 30min and reperfused for 180min plus administration of SP600125, inhibitor of JNK[6mg/kg i.p. 2h before operation. SP600125 was dissolved in 100µl DMSO] (n=12); 5.LAD was occluded for 30min and reperfused for 180min plus administration of DMSO[100µl DMSO i.p. 2h before operation.] (n=12). |
Dosage form | 10mg/kg; i.v. |
Applications | Fasudil reduced cell apoptosis in I/R in vivo via suppression of c-Jun N-terminal kinase(JNK)-mediated apoptosis-inducing factor(AIF) translocation. |
References: [1]Abe H, Kamai T, Hayashi K, et al. The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells[J]. BMC cancer, 2014, 14: 1-12. [2]Zhang J, Li X X, Bian H J, et al. Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIF translocation[J]. Clinica Chimica Acta, 2009, 401(1-2): 76-80. | |
| 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 | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 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 |
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- Purity: >98.00%
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