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

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEFasudildihydrochlorideCat.No.:HY-10341CCASNo.:203911-27-7Synonyms:HA-1077dihydrochloride;AT-877dihydrochloride分?式:C??H??Cl?N?O?S分?量:364.29作?靶點(diǎn):CalciumChannel;ROCK;PKA;PKC;Autophagy;HIV作?通路:MembraneTransporter/IonChannel;NeuronalSignaling;CellCycle/DNADamage;Cytoskeleton;StemCell/Wnt;TGF-beta/Smad;Epigenetics;Autophagy;Anti-infection儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Fasudil(HA-1077;AT877)dihydrochloride?種?特異性RhoA/ROCK抑制劑，并抑制蛋?激酶。Fasudildihydrochloride抑制ROCK1的Ki為0.33μM，抑制ROCK2，PKA，PKC，PKG的IC50分別為0.158μM和4.58μM，12.30μM，1.650μM。Fasudildihydrochloride也?種有效的Ca2+通道拮抗劑和?管擴(kuò)張劑。IC50&TargetPKAPKCp160ROCKROCK24.58μM(IC50)12.3μM(IC50)0.33μM(Ki)0.158μM(IC50)PKG1.65μM(IC50)體外研究Fasudildihydrochloride(100μM)inhibitscellspreading,theformationofstressfibers,andexpressionofα-SMAwithconcomitantsuppressionofcellgrowthinratHSCs(hepaticstellatecells)andhumanHSC-derivedTWNT-4cells[4].Fasudildihydrochloride(50-100μM;24hours)inhibitstheLPA(lysophoaphatidicacid)-inducedphosphorylationofERK1/2,JNK,andp38detectedbywesternblottinginratHSCsandhumanHSC-derivedTWNT-4cells[4].Fasudildihydrochloride(25-100μM;24hours)suppressestranscriptionofcollagenandTIMP,stimulatestranscriptionofMMP-1inhumanHSC-derivedTWNT-4cells[4].WesternBlotAnalysis[4]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:RatHSCsandhumanHSC-derivedTWNT-4cellsConcentration:50μM;100μMIncubationTime:24hoursResult:SuppressedtheLPA-inducedphosphorylationofERK1/2,JNKandp38MAPKby60%,70%,and90%,respectively.RT-PCR[4]CellLine:RatHSCsandhumanHSC-derivedTWNT-4cellsConcentration:25μM;50μM;100μMIncubationTime:24hoursResult:ReducedtheexpressionoftypeIcollagen,a-SMA,andTIMP-1.體內(nèi)研究Fasudildihydrochloride(10mg/kg;i.v.;1hbeforeoperation)exhibitsprotectableeffectsoncardiovasculardiseaseandreducestheactivationofJNKandattenuatesmitochondrial-nucleartranslocationofAIFunderischemicinjury[5].Fasudildihydrochloride(50mg/kg/d;i.p.)inhibitsacuteandrelapsingEAE(experimentalautoimmuneencephalomyelitis)inducedbyproteolipidproteinPLPp139-151,reduceslymphocytesproliferation,resultsdownregulationofinterleukin(IL)-17andamarkeddecreaseoftheIFN-γ/IL-4ratio[6].Fasudildihydrochloride(100mg/kg/d;p.o.)significantlyreducesincidenceandpathologicalexaminationscoreofEAE(experimentalautoimmuneencephalomyelitis)inSJL/Jmice,decreasesinflammation,demyelination,axonallossandAPPpositiveinspinalcordinmice[6].AnimalModel:Myocardialischemiaandreperfusioninrat(250-300g)[5]Dosage:10mg/kgAdministration:Intravenousinjection;1hbeforeoperationResult:ActivatedtheRho-kinase,JNK,andresultedAIFtranslocatedtothenucleus.InhibitedRho-kinaseactivity,andreducedmyocardialinfarctsizeandheartcellapoptosis.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?JExpClinCancerRes.2020Jun16;39(1):113.?ClinTranslMed.2022Jul;12(7):e961.?NeuralRegenRes.2021Dec;16(12):2512-2520.?SciRep.2018Feb6;8(1):2477.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].ChenM,etal.Fasudilanditsanalogs:anewpowerfulweaponinthelongwaragainstcentralnervoussystemdisorders?ExpertOpinInvestigDrugs.2013Apr;22(4):537-50.[2].HuangXN,etal.Theeffectsoffasudilonthepermeabilityoftheratblood-brainbarrierandblood-spinalcordbarrierfollowingexperimentalautoimmuneencephalomyelitis.JNeuroimmunol.2011Oct28;239(1-2):61-7.[3].UehataM,etal.CalciumsensitizationofsmoothmusclemediatedbyaRho-associatedproteinkinaseinhypertension.Nature.1997Oct30;389(6654):990-4.[4].FukushimaM,etal.Fasudilhydrochloridehydrate,aRho-kinase(ROCK)inhibitor,suppressescollagenproductionandenhancescollagenaseactivityinhepaticstellatecells.LiverInt.2005Aug;25(4):829-38.[5].ZhangJ,etal.InhibitionoftheactivityofRho-kinasereducescardiomyocyteapoptosisinheartischemia/reperfusionviasuppressingJNK-mediatedAIFtranslocation.ClinChimActa.2009Mar;401(1-2):76-80.[6].SunX,etal.TheselectiveRho-kinaseinhibitorFasudilisprotectiveandtherapeuticinexperimentalautoimmuneencephalomyelitis.JNeuroimmunol.2006Nov;180(1-2):12