Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESU5402Cat.No.:HY-10407CASNo.:215543-92-3分?式:C??H??N?O?分?量:296.32作?靶點:VEGFR;FGFR;PDGFR作?通路:ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥30mg/mL(101.24mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.3747mL16.8736mL33.7473mL5mM0.6749mL3.3747mL6.7495mL10mM0.3375mL1.6874mL3.3747mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(8.44mM);ClearsolutionBIOLOGICALACTIVITY?物活性SU5402?種有效的多靶點受體酪氨酸激酶抑制劑，作?于VEGFR2，F(xiàn)GFR1和PDGFRβ，IC50分別為20nM，30nM和510nM。IC50&TargetVEGFR2FGFR1PDGFRβ20nM(IC50)30nM(IC50)510nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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