GW788388-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGW788388Cat.No.:HY-10326CASNo.:452342-67-5分⼦式:C₂₅H₂₃N₅O₂分⼦量:425.48作⽤靶点:TGF-βReceptor作⽤通路:TGF-beta/Smad储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(58.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3503mL11.7514mL23.5029mL5mM0.4701mL2.3503mL4.7006mL10mM0.2350mL1.1751mL2.3503mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，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件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.88mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.88mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.88mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GW788388⼀种有效的ALK5抑制剂，IC50值18nM；同时抑制TGF-βII型受体和激活素II型受体的活性，但对BMPII型受体⽆作⽤。IC50&TargetIC50:18nM(ALK5)体内研究GW788388givenorallyfor5weekssignificantlyreducesrenalfibrosisanddecreasedthemRNAlevelsofkeymediatorsofextracellularmatrixdepositioninkidneysindb/dbmice[1].GW788388(50mg/kg/day,p.o.)significantlyattenuatessystolicdysfunctionintheMIanimals,togetherwiththeattenuationoftheactivated(phosphorylated)Smad2(P<0.01),α-smoothmuscleactin(P<0.001),andcollagenI(P<0.05)inthenoninfarctzoneofMIrats[2].GW788388reducestheexpressionofcollagenIA1by80%atadoseof1mg/kgtwiceaday(b.i.d.).GW788388significantlyreducestheexpressionofcollagenIA1mRNAwhenadministeredorallyat10mg/kgonceaday(u.i.d.)inamodelofpuromycinaminonucleoside-inducedrenalfibrosis[3].PROTOCOLAnimalOneweekpostsurgery,sham-operated(N=6)andinfarctedanimals(N=10)arerandomizedtotreatmentwithAdministration[2]theALK5inhibitorGW788388(GSK)atadosageof50mg/kg/daybygavage,whichhasbeenshowntosignificantlyattenuatecollagenoverexpressioninarodentmodelofdimethylnitrosamine-inducedliverdisease.Untreatedrats,thatis,sham-operated(N=9)andMIanimals(N=15),aregavagedwithvehicle(1%carboxymethylcellulosesolution).Fouranimalswith<25%infarctsizeasdeterminedpostmortembyhistologyareexcludedfromfurtheranalyses.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellProlif.2021Jan;54(1):e12933.•IntJMolSci.2022,23(20),12219.•OrgLett.2020Aug7;22(15):5726-5730.•OrgLett.2017Jan6;19(1):286-289.•LabInvest.2019Jul;99(8):1173-1192.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].PetersenM,etal.OraladministrationofGW788388,aninhibitorofTGF-betatypeIandIIreceptorkinases,decreasesrenalfibrosis.KidneyInt,2008,73(6),705-715.[2].TanSM,etal.Targetedinhibitionofactivinreceptor-likekinase5signalingattenuatescardiacdysfunctionfollowingmyocardialinfarction.AmJPhysiolHeartCircPhysiol,2010,298(5),H1415-1425.[3].GellibertF,etal.Discoveryof4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H-pyran-4-yl)benzamide(GW788388):apotent,selective,andorallyactivetransforminggrowthfactor-betatypeIreceptorinhibitor.JMedChem.2006,49McePdfHeightCaution:Produ