Fasudil (HA-1077) HCl |
| رقم الكتالوجGC14289 |
Fasudil (HA-1077؛ AT877) Hydrochloride هو مثبط RhoA / ROCK غير محدد وله أيضًا تأثير مثبط على كينازات البروتين ، مع Ki 0.33 μ ؛ M لـ ROCK1 ، IC50s من 0.158 μ ؛ M و 4.58 &88 ، 128888956 ؛ ؛ M ، 1.650 μ ؛ M لـ ROCK2 و PKA ، PKC ، PKG ، على التوالي. Fasudil (HA-1077) حمض الهيدروكلوريك هو أيضًا مضاد فعال لقناة Ca2+ وموسع للأوعية.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 105628-07-7
Sample solution is provided at 25 µL, 10mM.
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Fasudil (HA-1077) HCl 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.
| 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: | |
| Cas No. | 105628-07-7 | SDF | |
| Chemical Name | 5-(1,4-diazepan-1-ylsulfonyl)isoquinoline;hydrochloride | ||
| Canonical SMILES | C1CNCCN(C1)S(=O)(=O)C2=CC=CC3=C2C=CN=C3.Cl | ||
| Formula | C14H17N3O2S.HCl | M.Wt | 327.83 |
| الذوبان | ≥ 16.4mg/mL in DMSO, ≥ 4.81 mg/mL in EtOH with ultrasonic, ≥ 50 mg/mL in Water | Storage | Store at 4°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.0504 mL | 15.2518 mL | 30.5036 mL |
| 5 mM | 610.1 μL | 3.0504 mL | 6.1007 mL |
| 10 mM | 305 μL | 1.5252 mL | 3.0504 mL |
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 14 reference(s) in Google Scholar.)
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