Semaxinib-SU5416-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESemaxinibCat.No.:HY-10374CASNo.:204005-46-9Synonyms:SU5416分⼦式:C₁₅H₁₄N₂O分⼦量:238.28作⽤靶点:VEGFR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DMF:50mg/mL(209.84mM;Needultrasonic)DMSO:20mg/mL(83.93mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM4.1967mL20.9837mL41.9674mL5mM0.8393mL4.1967mL8.3935mL10mM0.4197mL2.0984mL4.1967mL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:2.25mg/mL(9.44mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Semaxinib(SU5416)有效，选择性的VEGFR(Flk-1/KDR)抑制剂，IC50为1.23μM[1]。IC50&TargetFlk-11.23μM(IC50)体外研究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].体内研究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—您⾝边的抑制剂⼤师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.户使⽤本产品发表的科研⽂献•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