盐酸法舒地尔作用机制 - Medchemexpress - MCE中国

1、Product Data SheetFasudil HydrochlorideCat. No.: HY-10341CAS No.: 105628-07-7分式: CHClNOS分量: 327.83作靶点: ROCK; Calcium Channel; Autophagy; PKA; PKC; HIV作通路: Cell Cycle/DNA Damage; Cytoskeleton; Stem Cell/Wnt; TGF-beta/Smad;Membrane Transporter/Ion Channel; Neuronal Signaling; Autophagy; ProteinTyrosin

2、e Kinase/RTK; Epigenetics; Anti-infection储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 H2O : 55 mg/mL (167.77 mM; Need ultrasonic)DMSO : 31 mg/mL (94.56 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 3.0504 mL 15.2518 mL

3、30.5036 mL5 mM 0.6101 mL 3.0504 mL 6.1007 mL10 mM 0.3050 mL 1.5252 mL 3.0504 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条

4、件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (6.34 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.08 mg/mL (6.34 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 40

5、0 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (6.34 mM); Clear solution此案可获得 2.08 mg/mL (6.34 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄均匀。DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合3. 请依序添加每种溶剂： 10% DMSO 9

6、0% corn oilSolubility: 2.08 mg/mL (6.34 mM); Clear solution此案可获得 2.08 mg/mL (6.34 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Fasudil Hydrochloride (HA-1077 Hydrochloride; AT877 Hydrochloride) 种特异性 ROCK 抑制剂，对蛋激酶也 有抑制作，ROCK1 的 K

7、i 值为 0.33 M，ROCK2 和 PKA，PKC，PKG 的 IC50 值分别 0.158 M 和 4.58 M，12.30 M，1.650 M。Fasudil Hydrochloride 也 种有效的 Ca2+ 通道拮抗剂和管扩张剂。IC & Target p160ROCK ROCK2 PKA PKC0.33 M (Ki) 0.158 M (IC50) 4.58 M (IC50) 12.30 M (IC50)PKG1.65 M (IC50)体外研究Fasudil Hydrochloride (100 M) inhibits cell spreading, the formation o

8、f stress fibers, and expression of -SMA withconcomitant suppression of cell growth in rat HSCs and human HSC-derived TWNT-4 cells4.Fasudil Hydrochloride (50-100 M; 24 hours) inhibits the LPA-induced phosphorylation of ERK1/2, JNK, and p38detected by western blotting in rat HSCs and human HSC-derived

9、 TWNT-4 cells4.Fasudil Hydrochloride (25-100 M; 24 hours) suppresses transcription of collagen and TIMP, stimulates transcriptionof MMP-1 in human HSC-derived TWNT-4 cells4.Western Blot Analysis4Cell Line: Rat HSCs and human HSC-derived TWNT-4 cellsConcentration: 50 M; 100 MIncubation Time: 24 hours

10、Result: Suppressed the LPA-induced phosphorylation of ERK1/2, JNK and p38 MAPK by 60%,70%,and 90%, respectively.RT-PCR4Cell Line: Rat HSCs and human HSC-derived TWNT-4 cellsConcentration: 25 M; 50 M; 100 M 24 hoursIncubation Time: 24 hoursPage 2 of 3 www.MedChemEResult: Reduced the expression of typ

11、e I collagen, a-SMA, and TIMP-1.体内研究 Fasudil (30 g) increases CBF by 50% via intra-coronary injection to dogs. Fasudil (0.01, 0.03, 0.1 and 0.3 mg/kg, bolus,i.v.) decreases MBP and increases HR, VBF, CBF, RBF, and FBF. Fasudil (1.0 ng/mL) increases cardiac output. Fasudil viai.v. produces a signific

12、ant fall in MBP, left ventricular systolic pressure and total peripheral resistance with an increasein HR and cardiac output, but without obvious effect on right atrial pressure, dP/dt or left ventricular minute work indogs3. Fasudil exhibits protectable effects on cardiovascular disease and reduces

13、 the activation of JNK andattenuates mitochondrial-nuclear translocation of AIF under ischemic injury6. Fasudil (100 mg/kg/day, p.o.)significantly reduces incidence and mean maximum clinical score of EAE in SJL/J mice immunized with PLP p139-151.Fasudil inhibits the proliferative response of splenoc

14、ytes to the antigen in mice. Fasudil decreases inflammation,demyelination, axonal loss and APP positivein spinal cord of Fasudil-treated mice via p.o. administration7.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Sci Rep. 2018 Feb 6;8(1):2477. Adipocyte. 2019 Dec;8(1):114-124. Tran

15、slational Neuroscience. 2020 May. Biomed Rep. 2015 May;3(3):361-364.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Chen M, et al. Fasudil and its analogs: a new powerful weapon in the long war against central nervous system disorders? Expert Opin Investig Drugs.2013

16、 Apr;22(4):537-50.2. Huang XN, et al. The effects of fasudil on the permeability of the rat blood-brain barrier and blood-spinal cordbarrier following experimentalautoimmune encephalomyelitis. J Neuroimmunol. 2011 Oct 28;239(1-2):61-7.3. Uehata M, et al. Calcium sensitization of smooth muscle mediat

17、ed by a Rho-associated protein kinase in hypertension. Nature. 1997 Oct30;389(6654):990-4.4. Fukushima M, et al. Fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity inhepatic stellate cells. Liver Int. 2005 Aug;25(4):829-38.5

18、. Corbin KD, et al. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol. 2012Mar;28(2):159-65.6. Zhang J, et al. Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIFtranslocation. Clin Chim Acta. 2009 Mar;401(1-2):76-80.7. Sun X, et al. The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol.2006