SU-5402-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESU5402Cat.No.:HY-10407CASNo.:215543-92-3分⼦式:C₁₇H₁₆N₂O₃分⼦量:296.32作⽤靶点:VEGFR;FGFR;PDGFR作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥30mg/mL(101.24mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.3747mL16.8736mL33.7473mL5mM0.6749mL3.3747mL6.7495mL10mM0.3375mL1.6874mL3.3747mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.44mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性SU5402⼀种有效的多靶点受体酪氨酸激酶抑制剂，作⽤于VEGFR2，FGFR1和PDGFRβ，IC50分别为20nM，30nM和510nM。IC50&TargetVEGFR2FGFR1PDGFRβ20nM(IC50)30nM(IC50)510nM(IC50)体外研究SU5402iscocrystallizedwiththecatalyticdomainofFGF-R1(flg-1)andisfoundtoinhibittyrosinephosphorylationofVEGF-R2(Flk-1/KDR)andPDGF-RinNIH3T3cellswithIC50valuesof0.4and60.9μM,respectively[1].InordertoinvestigatewhetherphosphorylationofPKM2andLDHAismediatedinFGFR1-specificmanner,FTC-133aretreatedwithreceptortyrosinekinaseinhibitorsDovitinibandSU5402(SU-5402).Dovitinibtreatmentresultsinsignificantdecreaseofphosphorylationstatusataconcentrationof100nMafterfourhoursofincubationforbothPKM2andLDHA.Nosignificantchangesareseenwhenadministeredatconcentrationsof1nMand10nM.SU5402administrationleadstoasigificantdecreaseofPKM2andLDHAphosphorylationataconcentrationof20μM[2].体内研究InhibitionofFGFR1withSU5402(SU5402)administeredtoΔF508-CFTRhomozygousmiceresultsinpartialΔF508-CFTRrescue,asshownbyanincreaseinsalivasecretion,asurrogate"sweattest"assayinmice.Assalivarysecretionisoftensexdependent,onlymalemicearechosenfortheseexperiments.OurresultsindicatethattreatmentoftheΔF508-CFTRmicewithSU5402restoresthesalivasecretionlevelto~10%ofthatobservedforthewild-typeCFTRmice,whichsuggeststhatSU5402canhavetherapeuticbenefitstoCysticFibrosis(CF)[3].TheselectiveFGFR1inhibitorSU5402(SU5402)preventsand/orreversesPHinducedbyMCT(monocrotaline)inrats.InratstreatedwithSU5402ondays21to42aftertheMCTinjection,evaluationsonday42showmarkeddecreasesinpulmonaryarterypressure(PAP),RV/(LV+S),anddistalarterymuscularizationcomparewithratstreatedwiththevehicle(saline)[4].PROTOCOLCellAssay[2]8505CandFTC133cellsaregrowninDMEM/F12suppplementedwith10%FCSand1%PenStrepandincubatedat37°C,5%CO2.ForB-CPAPRPMI1640mediumisused.FGFR1inhibitionexperimentsareperformedonFTC133cellsbyemploymentofReceptorTyrosineKinaseInhibitorsTKI-258(Dovitinib)andSU5402(20μM).Inhibitionisconductedover4hwiththeindicatedinhibitorconcentrations.ControlcellsreceivecorrespondingconcentrationsofDMSO[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3][4]MaleΔF508mice(CFTRtm1Eurona129/FVBbackground)andtheirwild-typelittermatesof9-12weeksareintraperitoneallyinjectedwithDMSOorSU5402(dissolvedinDMSOattheconcentrationof6mg/mL)at252/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEmg/kgbodyweight,everydayfor1week.Themiceareweigheddailyandthedosagesadjustedaccordingly.Themicearethenanesthetizedbyinhalingisofluraneuntiltheendoftheprocedure.Cholinergicantagonist,Atropine(1mM,50μL)issubcutaneouslyinjectedintotherightcheektoblockpotentialcholinergicstimulationofthesalivarygland.Asmallstripoffilterpaperisplacedagainsttheinjectedcheek,for4min.Isoprenaline(10mM,37.5μL)issubsequentlyinjectedinthesamespottostimulateanadrenergicsecretionofsaliva(time0).Filterstrips(pre-weighedinanEppendorftube)arereplacedevery5min,overaperiodof30min.Allsixfilterstripsareweighedattheendofthecollectionandtheresultsarenormalizedrelativetomg/gbodyweight.Rats[4]ToassessthepotentialeffectsoftheFGFR1inhibitorSU5402onestablishedPH,adultmaleWistarrats(200-250g)aregivenMCT(60mg/kgs.c.),leftuntreatedfor21days,thenrandomlydividedinto2groups(10animalsineachgroup),ofwhichoneistreatedwithSU5402(25mg/kg/day)andtheothergiventhevehicle,fromday21today42.Alltreatmentsaregivenonceadaybys.c.injection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JHazardMater.2020Jul5;393:122440.•iScience.2019Sep27;19:1248-1259.•Theriogenology.2019Jul1;132:27-35.•Theriogenology.2019Nov;139:90-97.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SunL,etal.Design,synthesis,andevaluationsofsubstituted3-[(3-or4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-onesasinhibitorsofVEGF,FGF,andPDGFreceptortyrosinekinases.JMedChem.1999Dec16;42(25):5120-30.[2].KachelP,etal.PhosphorylationofpyruvatekinaseM2andlactatedehydrogenaseAbyfibroblastgrowth