Semaxinib-SU5416-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESemaxinibCat.No.:HY-10374CASNo.:204005-46-9Synonyms:SU5416分?式:C??H??N?O分?量:238.28作?靶點:VEGFR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DMF:50mg/mL(209.84mM;Needultrasonic)DMSO:20mg/mL(83.93mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM4.1967mL20.9837mL41.9674mL5mM0.8393mL4.1967mL8.3935mL10mM0.4197mL2.0984mL4.1967mL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?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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:2.25mg/mL(9.44mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Semaxinib(SU5416)有效，選擇性的VEGFR(Flk-1/KDR)抑制劑，IC50為1.23μM[1]。IC50&TargetFlk-11.23μM(IC50)體外研究Semaxinib(SU5416)inhibitsVEGF-drivenmitogenesisinadose-dependentmannerwithanIC50of0.04±0.02μM(n=3).Incontrast,Semaxinib(SU5416)blocksFGF-dependentmitogenesisofHUVECswithanIC50of50μM(n=10).AnIC50of20.26±5.2μM,whichisabout20-foldlessinpotencyonPDGF-dependentautophosphorylation,isobservedwhenSU5416istestedinNIH3T3cellsoverexpressingthehumanPDGFreceptorβ[1].體內(nèi)研究DailyadministrationofSemaxinib(SU5416)(i.p.,3mg/kg/day)inhibitsthelocalgrowthofC6tumorsinthecolon.Acomparablelevelofgrowthinhibition(62%byday16;P=0.001)isobservedfortumorsgrowinginthecolonincomparisonwithonesgrowinginthehindflankregion(54%byday18;P=0.001).TheseresultsindicatethatSemaxinib(SU5416)couldinhibittumorgrowthatasiteotherthanthesubcutaneousimplantationsite,wherethepreexistingvasculaturemaybedifferent[1].DailytreatmentwithSemaxinib(SU5416)(25mg/kg)resultsinasignificantlylowertumorgrowthratewithtumormassesofupto8%ofthatpresentincontrolanimalsbyday22afterimplantation.InhibitionoftumorgrowthisclearlyprecededbyamarkedreductionofthetissueareacoveredbythenewlyformedgliomamicrovasculatureintheSemaxinib-treatedgroup,indicatingareducedinitialtumorvascularization[2].PROTOCOLCellAssay3T3Her2and488G2M2areNIH3T3fibroblastcelllinesengineeredtooverexpressHer2andtoexpresshumanPDGF-BBandhumanPDGFreceptorβ.BothcelllinesareculturedinDMEMsupplementedwith2%CSand2mML-glutamine.C6,Calu6,A375,A431,andSF767Tareplatedintheirrespectivegrowthmediumat2×103cells/100μL/wellin96-well,flat-bottomedplates.Semaxinib(SU5416)isseriallydilutedinmediacontainingDMSO(50sarecalculatedbycurvefittingusingfour-parameteranalysis[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1][3]FemaleBALB/cnu/numice(20-22g;12weeksofage)areused.Aseptictechniqueisusedduringthissurgicalprocedure.Asmallmidlineincision(1cm)ismadeintheabdomendirectlyoverthecolon.C6cellsareimplanted(0.5×106cells/animal)undertheserosaofthecolonusinga27-gaugeneedle.Afterimplantation,allexposedsectionsoftheintestinearereturnedintotheabdominalcavity.Theperitoneumandskinareclosedusinga6.0surgicalsutureandwoundclips.Thewoundclipsareremoved7daysaftersurgery.Animalsaretreatedoncedailywitha50μLi.p.bolusinjectionofeitherSemaxinib(SU5416)or2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDMSO,beginning1dayafterimplantation.Approximately13-16daysafterimplantation,animalsareeuthanized,andlocaltumorgrowthonthecolonisquantitatedeitherbyweighingthetumorsorbymeasuringthetumorsusingveniercalipers.Tumorvolumesarecalculatedastheproductoflength×width×height.Rats[3]MaleSpragueDawleyrats(n=60,6-8wk)arerandomlydividedamongfivegroups:control(Con),Semaxinib(SU),pneumonectomy(PNx),Semaxinib+hypoxia(SuHx),andSemaxinib+PNx(SuPNx).TheSuHxprotocolisemployed.Briefly,animalsareinjectedwithSemaxinib(25mg/kg)dissolvedincarboxymethylcellulose(CMC)andexposedtohypoxia(10%)for4wkfollowedbyre-exposuretonormoxia.PNxanimalsunderwentaleftpneumonectomy.TwodaysfollowingPNxsurgeryaninjectionofSemaxinibisadministered(25mg/kg).TheCongroupreceivedonlythesolventCMC.Echocardiographyisutilizedatbaseline(prehypoxia/presurgery),week2,andweek6todeterminecardiacmorphometryandfunction.Twoandsixweekspostsurgery/posthypoxiaanimalsareanesthetizedandrightventricle(RV)andleftventricle(LV)pressuremeasurementsviacatheterizationareperformed.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?AdvFunctMater.2021May24.?NatCommun.2021Oct26;12(1):6177.?Hypertension.2021Sep27;HYPERTENSIONAHA12016712.?BrJPharmacol.2021Oct2.?CellChemBiol.2022Jun9;S2451-9456(22)00201-X.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].FongTA,etal.SU5416isapotentandselectiveinhibitorofthevascularendothelialgrowthfactorreceptor(Flk-1/KDR)thatinhibitstyrosinekinasecatalysis,tumorvascularization,andgrowthofmultipletumortypes.CancerRes,1999,59(1),99-106.[2].VajkoczyP,etal.Inhibitionoftumorgrowth,angiogenesis,andmicrocirculationbythenovelFlk-1inhibitorSU5416asasses