Tivozanib-AV-951-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETivozanibCat.No.:HY-10977CASNo.:475108-18-0Synonyms:AV-951;KRN951分⼦式:C₂₂H₁₉ClN₄O₅分⼦量:454.86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DMSO:25mg/mL(54.96mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1985mL10.9924mL21.9848mL5mM0.4397mL2.1985mL4.3970mL10mM0.2198mL1.0992mL2.1985mL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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.50mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Tivozanib(AV-951;KRN951)⼀种有效的、选择性的、具有⼝服活性的VEGFR酪氨酸激酶抑制剂，对VEGFR-1、VEGFR-2、VEGFR-3的IC50值分别为0.21、0.16、0.24nM。Tivozanib抑制肿瘤组织中的⾎管⽣成和⾎管通透性，并显⽰出抗肿瘤活性。Tivozanib具有研究转移性肾细胞癌(RCC)的潜⼒[1][2][3]。IC50&TargetVEGFR1VEGFR2VEGFR30.21nM(IC50)0.16nM(IC50)0.24nM(IC50)体外研究TivozanibinhibitsthephosphorylationofVEGFR-1,VEGFR-2andVEGFR-3[2].体内研究Tivozanib(1mg/kg;p.o.;14days)suppressesthedevelopmentofCNVlesionsandledstoasignificantregressionofestablishedCNV,reducingtheaffectedareasby67.7%[4].PROTOCOLKinaseAssayCell-freekinaseassaysaredoneinquadruplicatewith1μMATPtodeterminetheIC50valuesofKRN951againstavarietyofrecombinantreceptorandnonreceptortyrosinekinases[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]Cell-basedassaysaredonetodeterminetheabilityofKRN951toinhibitligand-dependentphosphorylationofreceptortyrosinekinases.Briefly,thecellsarestarvedovernightinappropriatebasicmediumcontaining0.5%fetalbovineserum(FBS).FollowingtheadditionofKRN951or0.1%DMSO,thecellsareincubatedfor1hourandthenstimulatedwiththecognateligandat37°C.Receptorphosphorylationisinducedfor5minutesexceptforVEGFR3(10minutes),c-Met(10minutes),andc-Kit(15minutes).Alltheligandsusedintheassaysarehumanrecombinantproteins,exceptforVEGF-C,aratrecombinantprotein.Followingcelllysis,receptorsareimmunoprecipitatedwithappropriateantibodiesandsubjectedtoimmunoblottingwithphosphotyrosine.QuantificationoftheblotsandcalculationofIC50valuesarecarriedout[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Cancercellsares.c.inoculatedintotherightflankoftheathymicrats.Onceestablished,tumorsofAdministration[1]1,500mm3aresurgicallyexcisedandsmallertumorfragments(20-30mg)ares.c.implantedintherightflankofirradiatedrats.OraladministrationofKRN951(0.2or1mg/kg)orvehicleisinitiatedatthedayofrandomization(day0).TumorvolumeismeasuredtwiceweeklywithVerniercalipers,andcalculated[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•CancerCellInt.2021Jun5;21(1):291.•TechnicalUniversityofMunich.24.01.2018.•Patent.US20170349880A1.•HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].MotzerRJ,etal.Tivozanibversussorafenibasinitialtargetedtherapyforpatientswithmetastaticrenalcellcarcinoma:resultsfromaphaseIIItrial.JClinOncol.2013Oct20;31(30):3791-9.[2].DeLucaA,etal.Tivozanib,apan-VEGFRtyrosinekinaseinhibitorforthepotentialtreatmentofsolidtumors.IDrugs.2010Sep;13(9):636-45.[3].EskensFA,detal.Biologicandclinicalactivityoftivozanib(AV-951,KRN-951),aselectiveinhibitorofVEGFreceptor-1,-2,and-3tyrosinekinases,ina4-week-on,2-week-offscheduleinpatientswithadvancedsolidtumors.ClinCancerRes.2011Nov15;17(22):7156-63.[4].KangS,etal.Antiangiogeniceffectsoftivozanib,anoralVEGFreceptortyrosinekinaseinhibitor,onexperimentalchoroidalneovascularizationinmice.ExpEyeRes.