更新于：2024-05-01
Fasudil mesylate
甲磺酸法舒地尔
更新于：2024-05-01
概要
基本信息
非在研机构- |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国) |
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结构
分子式C15H21N3O5S2 |
InChIKeyMVCDPGYHRHUECK-UHFFFAOYSA-N |
CAS号1001206-62-7 |
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关联
10
项与 甲磺酸法舒地尔 相关的临床试验A Phase 1 study of Fasudil in combination with Methotrexate, Adriamycin and Cisplatin (MAP) targeting cancer stem cell.
A Phase 2a Open-Label Preliminary Safety, Efficacy, and Biomarker Study of WP-0512 in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2a Open-Label Preliminary Safety, Tolerability, and Biomarker Study of Oral Fasudil in Patients With the 4-Repeat Tauopathies of Progressive Supranuclear Palsy-Richardson Syndrome or Corticobasal Syndrome.
100 项与 甲磺酸法舒地尔 相关的临床结果
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100 项与 甲磺酸法舒地尔 相关的转化医学
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100 项与 甲磺酸法舒地尔 相关的专利（医药）
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1,198
项与 甲磺酸法舒地尔 相关的文献（医药）2024-02-20Animal models and experimental medicine
"Baihui" (DU20)-penetrating "Qubin" (GB7) acupuncture on blood-brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK II/MLC 2 signaling pathway.
Article
作者: Ce Zhang ; Jia Zheng ; Xueping Yu ; Binglin Kuang ; Xiaohong Dai ; Lei Zheng ; Weiwei Yu ; Wei Teng ; Hongtao Cao ; Mingyue Li ; Jiayong Yao ; Xiaoying Liu ; Wei Zou
BACKGROUND:
Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH.
METHODS:
Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point "Baihui"-penetrating "Qubin," and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging.
RESULTS:
We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at "Baihui"-penetrating "Qubin" and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats.
CONCLUSION:
This study found that these experimental data indicated that SA at "Baihui"-penetrating "Qubin" could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.
2024-02-01Neurochemistry international
Early chronic fasudil treatment rescues hippocampal alterations in the Ts65Dn model for down syndrome.
Article
作者: Rosa López-Hidalgo ; Raúl Ballestín ; Lorena Lorenzo ; Sandra Sánchez ; José Miguel Blasco-Ibáñez ; Carlos Crespo ; Juan Nacher ; Emilio Varea
Down syndrome (DS) is the most common genetic disorder associated with intellectual disability. To study this syndrome, several mouse models have been developed. Among the most common is the Ts65Dn model, which mimics most of the alterations observed in DS. Ts65Dn mice, as humans with DS, show defects in the structure, density, and distribution of dendritic spines in the cerebral cortex and hippocampus. Fasudil is a potent inhibitor of the RhoA kinase pathway, which is involved in the formation and stabilization of dendritic spines. Our study analysed the effect of early chronic fasudil treatment on the alterations observed in the hippocampus of the Ts65Dn model. We observed that treating Ts65Dn mice with fasudil induced an increase in neural plasticity in the hippocampus: there was an increment in the expression of PSA-NCAM and BDNF, in the dendritic branching and spine density of granule neurons, as well as in cell proliferation and neurogenesis in the subgranular zone. Finally, the treatment reduced the unbalance between excitation and inhibition present in this model. Overall, early chronic treatment with fasudil increases cell plasticity and eliminates differences with euploid animals.
2024-02-01Neurology. Genetics
Role of Rho-Associated Kinase in the Pathophysiology of Cerebral Cavernous Malformations.
Review
作者: Cenk Ayata ; Helen Kim ; Leslie Morrison ; James K Liao ; Juan Gutierrez ; Miguel Lopez-Toledano ; Enrique Carrazana ; Adrian L Rabinowicz ; Issam A Awad
Cerebral cavernous malformations (CCMs) are vascular lesions characterized by a porous endothelium. The lack of a sufficient endothelial barrier can result in microbleeds and frank intracerebral hemorrhage. A primary mechanism for lesion development is a sequence variant in at least 1 of the 3 CCM genes (CCM1, CCM2, and CCM3), which influence various signaling pathways that lead to the CCM phenotype. A common downstream process associated with CCM gene loss of function involves overactivation of RhoA and its effector Rho-associated kinase (ROCK). In this study, we review RhoA/ROCK-related mechanisms involved in CCM pathophysiology as potential therapeutic targets. Literature searches were conducted in PubMed using combinations of search terms related to RhoA/ROCK and CCMs. In endothelial cells, CCM1, CCM2, and CCM3 proteins normally associate to form the CCM protein complex, which regulates the functions of a wide variety of protein targets (e.g., MAP3K3, SMURF1, SOK-1, and ICAP-1) that directly or indirectly increase RhoA/ROCK activity. Loss of CCM complex function and increased RhoA/ROCK activity can lead to the formation of stress fibers that contribute to endothelial junction instability. Other RhoA/ROCK-mediated pathophysiologic outcomes include a shift to a senescence-associated secretory phenotype (primarily mediated by ROCK2), which is characterized by endothelial cell migration, cell cycle arrest, extracellular matrix degradation, leukocyte chemotaxis, and inflammation. ROCK represents a potential therapeutic target, and direct (fasudil, NRL-1049) and indirect (statins) ROCK inhibitors have demonstrated various levels of efficacy in reducing lesion burden in preclinical models of CCM. Current (atorvastatin) and planned (NRL-1049) clinical studies will determine the efficacy of ROCK inhibitors for CCM in humans, for which no US Food and Drug Administration-approved or EU-approved pharmacologic treatment exists.
100 项与 甲磺酸法舒地尔 相关的药物交易
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研发状态
| 适应症 | 最高研发状态 | 国家/地区 | 公司 |
|---|---|---|---|
| 颅内血管痉挛 | 批准上市 | 中国 更多 | |
| 大脑梗塞 | 批准上市 | 中国 更多 | |
| 肌萎缩侧索硬化 | 临床前 | 日本 更多 |
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临床结果
临床结果
适应症
分期
评价
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N/A | - | 構壓簾糧窪廠夢膚鹹醖(醖鑰窪構衊願製醖獵窪) = 積餘選糧網簾齋遞獵觸 壓構蓋窪獵襯艱齋齋壓 (獵製蓋齋遞蓋獵鑰膚繭 ) 更多 | 积极 | 2009-04-01 | |||
Vehicle | 構壓簾糧窪廠夢膚鹹醖(醖鑰窪構衊願製醖獵窪) = 網觸淵齋網壓艱範夢醖 壓構蓋窪獵襯艱齋齋壓 (獵製蓋齋遞蓋獵鑰膚繭 ) 更多 | ||||||
临床3期 | 17 | (40 mg Fasudil) | 鹹範壓製淵蓋夢願鏇觸(獵壓淵選窪餘醖鏇鹹廠) = 鬱齋鬱壓淵鹽鏇糧鏇衊 鏇衊繭夢糧膚淵鹹壓網 (獵夢鏇製遞窪襯憲衊築, 廠觸積遞築蓋壓獵夢鹽 ~ 網範網窪鹹積壓廠鹹製) 更多 | - | 2014-11-04 | ||
(Placebo) | 鹹範壓製淵蓋夢願鏇觸(獵壓淵選窪餘醖鏇鹹廠) = 膚顧鏇構繭廠蓋窪廠蓋 鏇衊繭夢糧膚淵鹹壓網 (獵夢鏇製遞窪襯憲衊築, 襯糧蓋齋淵膚網構繭憲 ~ 餘淵齋醖簾鹹壓壓鑰醖) 更多 | ||||||
N/A | 3 | (鏇鹽衊簾糧襯繭製觸廠) = 顧齋鬱鹽範築鏇積鹽觸 鹹簾遞窪襯顧鑰鏇糧遞 (簾襯範遞艱醖糧膚觸選, 10) 更多 | 积极 | 2014-10-19 |
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