Fasudil-HA-1077-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFasudilCat. No.: HY-10341ACAS No.: 103745-39-7Synonyms: HA-1077; AT877分式: CHNOS分量: 291.37作靶點(diǎn): ROCK; Calcium Channel; Autophagy作通路: Cell Cycle/DNA Damage; Stem Cell/Wnt; TGF-beta/Smad; Membrane Transporter/Ion Channel; Neuronal S

2、ignaling; Autophagy儲存式: Please store the product under the recommended conditions inthe COA.BIOLOGICAL ACTIVITY物活性 Fasudil (HA-1077; AT877)，種有效的 ROCK 抑制劑，對 ROCK1 的 Ki 值為 0.33 M，也種有效 Ca2+通道拮抗劑和管擴(kuò)張劑。IC50 & Target p160ROCK0.33 M (Ki)體外研究 Fasudil has vasodilatory action and occupies the adenine pocket o

3、f the ATP-binding site of the enzyme 1.Fasudil produces a competitive inhibition of the Ca2+-induced contraction of the depolarized rabbit aorta.Fasudil inhibits contractile responses to KCl, phenylephnne (PHE) and prostaglandin (PG) F2a 2. Fasudilalso exhibits vasodilator actions by inhibition of 5

4、-hydroxytryptamine, noradrenaline, histamine, angiotensin,and dopamine induced spiral strips contraction 3. In addition, Fasudil induces disorganization of actin stressfiber and cell migration inhibition 4. Fasudil inhibits hepatic stellate cells spreading, the formation of stressfibers, and express

5、ion of -SMA with concomitant suppression of cell growth, but does not induce apoptosis.Fasudil also blocks the LPA-induced phosphorylation of ERK1/2, JNK and p38 MAPK 5.體內(nèi)研究Fasudil (30 g) increases CBF by 50% via intra-coronary injection to dogs. Fasudil (0.01, 0.03, 0.1 and 0.3mg/kg, bolus, i.v.) d

6、ecreases MBP and increases HR, VBF, CBF, RBF, and FBF. Fasudil (1.0 ng/mL)increases cardiac output. Fasudil via i.v. produces a significant fall in MBP, left ventricular systolic pressureand total peripheral resistance with an increase in HR and cardiac output, but without obvious effect on rightatr

7、ial pressure, dP/dt or left ventricular minute work in dogs 3. Fasudil exhibits protectable effects on1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEcardiovascular disease and reduces the activation of JNK and attenuates mitochondrial-nuclear translocationof AIF under ischemic injury 6. Fasudil (1

8、00 mg/kg/day, p.o.) significantly reduces incidence and meanmaximum clinical score of EAE in SJL/J mice immunized with PLP p139-151. Fasudil inhibits the proliferativeresponse of splenocytes to the antigen in mice. Fasudil decreases inflammation, demyelination, axonal lossand APP positivein spinal c

9、ord of Fasudil-treated mice via p.o. administration 7.PROTOCOLKinase Assay 1 Cyclic AMP-dependent protein kinase activity is assayed in a reaction mixture containing, in a final volume of0.2 mL, 50 mM Tris-HCl (pH 7.0), 10 mM magnesium acetate, 2 mM EGTA, 1 M cyclic AMP or absence ofcyclic AMP, 3.3

10、to 20 M r-32P ATP (4105 c.p.m.), 0.5 g of the enzyme, 100 g of histone H2B andcompound. The mixture is incubated at 30C for 5 min. The reaction is terminated by adding 1mL of ice-cold20% trichloroacetic acid after adding 500 g of bovine serum albumin as a carrier protein. The sample iscentrifuged at

11、 3000 r.p.m. for 15min, the pellet is resuspended in ice-cold 10% trichloro-acetic acid solutionand the centrifugation-resuspension cycle is repeated three times. The final pellet is dissolved in 1 mL of 1 NNaOH and radioactivity is measured with a liquid scintillation counter 1.MCE has not independ

12、ently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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. Biomed Rep. 2015 May;3(3):361-364.See more customer validations on HYPERLINK / www.MedChemEREFER

13、ENCES1. Ono-Saito N, et al. H-series protein kinase inhibitors and potential clinical applications. Pharmacol Ther. 1999 May-Jun;82(2-3):123-31.2. Asano T, et al. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther. 1987 Jun;241(3):1033-40.3. Asano T, et al. Vasodilator a

14、ctions of HA1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase. Br J Pharmacol.1989 Dec;98(4):1091-100.4. Negoro N, et al. The kinase inhibitor fasudil (HA-1077) reduces intimal hyperplasia through inhibiting migration and enhancing cell lossof vascular smooth muscle c

15、ells. Biochem Biophys Res Commun. 1999 Aug 19;262(1):211-5.5. Fukushima M, et al. Fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, suppresses collagen production and enhancescollagenase activity in hepatic stellate cells. Liver Int. 2005 Aug;25(4):829-38.6. Zhang J, et al. Inhibition of

16、 the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressingJNK-mediated AIF translocation. 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. JNeuroimmunol. 2006 Nov;180(1-2):126-348. Uehata M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997 Oct30;389(6654):990-