Fasudil (HA-1077; AT877) dihydrochloride 是一种非特异性
RhoA/ROCK抑制剂，并抑制蛋白激酶。Fasudil dihydrochloride 抑制
ROCK1的
Ki为 0.33 μM，抑制
ROCK2，
PKA，
PKC，
PKG的
IC50分别为 0.158 μM 和 4.58 μM，12.30 μM，1.650 μM。Fasudil dihydrochloride 也是一种有效的 Ca
2+通道拮抗剂和血管扩张剂。
| 生物活性 |
Fasudil (HA-1077; AT877) dihydrochloride is a nonspecificRhoA/ROCKinhibitor and also has inhibitory effect on protein kinases, with anKiof 0.33 μM forROCK1,IC50s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM forROCK2andPKA,PKC,PKG, respectively. Fasudil dihydrochloride is also a potent Ca2+channel antagonist and vasodilator[1][2][3].
|
| IC50& Target |
PKA 4.58 μM (IC50) |
PKC 12.3 μM (IC50) |
p160ROCK 0.33 μM (Ki) |
ROCK2 0.158 μM (IC50) |
PKG 1.65 μM (IC50) |
|
体外研究
(In Vitro) |
Fasudil dihydrochloride (100 μM) inhibits cell spreading, the formation of stress fibers, and expression of α-SMA with concomitant suppression of cell growth in rat HSCs (hepatic stellate cells) and human HSC-derived TWNT-4 cells[4].
Fasudil dihydrochloride (50-100 μM; 24 hours) inhibits the LPA (lysophoaphatidic acid)-induced phosphorylation of ERK1/2, JNK, and p38 detected by western blotting in rat HSCs and human HSC-derived TWNT-4 cells[4].
Fasudil dihydrochloride (25-100 μM; 24 hours) suppresses transcription of collagen and TIMP, stimulates transcription of MMP-1 in human HSC-derived TWNT-4 cells[4].
Western Blot Analysis[4]
| Cell Line: |
Rat HSCs and human HSC-derived TWNT-4 cells |
| Concentration: |
50 μM; 100 μM |
| Incubation Time: |
24 hours |
| Result: |
Suppressed the LPA-induced phosphorylation of ERK1/2, JNK and p38 MAPK by 60%, 70%,and 90%, respectively. |
RT-PCR[4]
| Cell Line: |
Rat HSCs and human HSC-derived TWNT-4 cells |
| Concentration: |
25 μM; 50 μM; 100 μM |
| Incubation Time: |
24 hours |
| Result: |
Reduced the expression of type I collagen, a-SMA, and TIMP-1. |
|
体内研究
(In Vivo) |
Fasudil dihydrochloride (10 mg/kg; i.v.; 1 h before operation) exhibits protectable effects on cardiovascular disease and reduces the activation of JNK and attenuates mitochondrial-nuclear translocation of AIF under ischemic injury[5].
Fasudil dihydrochloride (50 mg/kg/d; i.p.) inhibits acute and relapsing EAE (experimental autoimmune encephalomyelitis) induced by proteolipid protein PLP p139-151, reduces lymphocytes proliferation, results downregulation of interleukin (IL)-17 and a marked decrease of the IFN-γ/IL-4 ratio[6].
Fasudil dihydrochloride (100 mg/kg/d; p.o.) significantly reduces incidence and pathological examination score of EAE (experimental autoimmune encephalomyelitis) in SJL/J mice, decreases inflammation, demyelination, axonal loss and APP positivein spinal cord in mice[6].
| Animal Model: |
Myocardial ischemia and reperfusion in rat (250-300 g)[5] |
| Dosage: |
10 mg/kg |
| Administration: |
Intravenous injection; 1 h before operation |
| Result: |
Activated the Rho-kinase, JNK, and resulted AIF translocated to the nucleus.
Inhibited Rho-kinase activity, and reduced myocardial infarct size and heart cell apoptosis. |
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| Clinical Trial |
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| 分子量 |
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| Formula |
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| CAS 号 |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
Please store the product under the recommended conditions in the Certificate of Analysis.
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