Sunitinib-SU-11248-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESunitinibCat.No.:HY-10255ACASNo.:557795-19-4Synonyms:SU11248分⼦式:C₂₂H₂₇FN₄O₂分⼦量:398.47作⽤靶点:VEGFR;PDGFR;IRE1;Mitophagy;Autophagy;Apoptosis作⽤通路:ProteinTyrosineKinase/RTK;CellCycle/DNADamage;Autophagy;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:20.83mg/mL(52.27mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5096mL12.5480mL25.0960mL5mM0.5019mL2.5096mL5.0192mL10mM0.2510mL1.2548mL2.5096mL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:≥1.11mg/mL(2.79mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.11mg/mL(2.79mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Sunitinib(SU11248)⼀种多靶点受体酪氨酸激酶抑制剂，抑制VEGFR2和PDGFRβ的IC50分别为80nM和2nM。SunitinibATP竞争性抑制剂，可通过抑制⾃⾝磷酸化和随后的RNase激活来有效抑制Ire1α的磷酸化。IC50&TargetVEGFR2PDGFRβ80nM(IC50)2nM(IC50)体外研究SunitinibMalateisalsoagoodinhibitorofKITandFLT-3[1].InRS4;11cells(FLT3-WT),treatmentwithSunitinib(SU11248)inhibitsFLT3-WTphosphorylationinadose-dependentmannerwithIC50ofapproximately250nM.InMV4;11cellsthatexpressFLT3-ITD,SunitinibinhibitsFLT3-ITDphosphorylationinadose-dependentmannerwithanIC50of50nMfollowinga2-hourtreatment[3].Inbiochemicalassays,Sunitinib(SU11248)exhibitscompetitiveinhibition(withregardtoATP)againstFlk-1andPDGFRβwithKivaluesof9nMand8nM,respectively.Sunitinibisalsoacompetitive,albeitlesspotent,inhibitorofFGFR1tyrosinekinaseactivity,withaKivalueof0.83μM.InadditiontothesethreestructurallyrelatedsplitkinasedomainRTKs,theactivityofSunitinibhasalsobeenevaluatedagainstabroadpanelofadditionaltyrosineandserine/threoninekinases.Inthesebiochemicalassays,theIC50valuesforSunitinibaregenerallyatleast10-foldhigherthanthoseforFlk-1andPDGFR(e.g.,IC50valuesof:>10μMforEGFRandCdk2;4μMforMet;2.4μMforIGFR-1;0.8μMforAbl;and0.6μMforSrc)[4].体内研究SunitinibMalatehasverygoodoralbioavailability,ishighlyefficaciousinanumberofpreclinicaltumormodels,andiswelltoleratedatefficaciousdoses[1].Sunitinib(80mg/kg/day)inhibitsthegrowthofestablishedSF763TandColo205tumorxenograftsinathymicmice.Sunitinib(SU11248)treatmenteffectivelyinhibitsthegrowthofestablishedtumorxenografts[4].PROTOCOLCellAssay[3]RS4;11andMV4;11celllinesarestarvedovernightinmediumcontaining0.1%FBSpriortoadditionofSunitinib(1nM,5nM,10nM,25nM,75nM,100nM,250nM,500nM)andFL(50ng/mL;FLT3-WTcellsonly).Proliferationismeasuredafter48hoursofcultureusingtheAlamarBlueassayintriplicateforeachcondition,asdescribedbythemanufacturer.Trypanbluecellviabilityassaysareperformedinparallelandyieldedsimilarresults[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2][4]Femalenu/numice(8-12weeksold,25grams)areused.Briefly,3-5×106o2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEthehindflankregionofmiceonday0.Dailytreatmentoftumor-bearingmicewithoraladministrationofSunitinibasacarboxymethylcellulosesuspensionorasacitratebuffered(pH3.5)solutionisinitiatedoncethetumorsreachedtheindicatedaveragesize.Tumorgrowthisevaluatedbasedontwice-weeklymeasurementoftumorvolume.Typically,studiesareterminatedwhentumorsinvehicle-treatedanimalsreachanaveragesizeof1000mm3orwhenthetumorsarejudgedtoadverselyeffectthewellbeingoftheanimals.Rats[4]AdultmaleWistarrats(325-349g)areused.Tovalidatetheabilityofthetime-lapseimagingmethodtoevaluatetheanti-angiogeniceffectsforagivendrugtreatment,twodrugstudiesareconducted.Inthefirststudy,mesentericwindowsareharvestedfromadultmaleWistarratsandculturedfor3daysaccordingtothetwoexperimentalgroups:1)10%serum(n=8tissuesfrom4rats),and2)10%serum+Sunitinib(5μM;n=8tissuesfrom4rats).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellMetab.2021Sep8;S1550-4131(21)00375-2.•NatBiomedEng.2018Aug;2(8):578-588.•Blood.2019Oct17;134(16):1323-1336.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•EMBOJ.2021Apr28;e106771.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SunL,etal.Discoveryof5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylicacid(2-diethylaminoethyl)amide,anoveltyrosinekinaseinhibitortargetingvascularendothelialandplatelet-derivedgrowthfactorr[2].AliMM,etal.StructureoftheIre1autophosphorylationcomplexandimplicationsfortheunfoldedproteinresponse.EMBOJ.2011Mar2;30(5):894-905.[3].O'FarrellAM,etal