Tivozanib-AV-951-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETivozanibCat.No.:HY-10977CASNo.:475108-18-0Synonyms:AV-951;KRN951分?式:C??H??ClN?O?分?量:454.86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DMSO:25mg/mL(54.96mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1985mL10.9924mL21.9848mL5mM0.4397mL2.1985mL4.3970mL10mM0.2198mL1.0992mL2.1985mL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?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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.50mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.50mM);ClearsolutionBIOLOGICALACTIVITY?物活性Tivozanib(AV-951;KRN951)?種有效的、選擇性的、具有?服活性的VEGFR酪氨酸激酶抑制劑，對VEGFR-1、VEGFR-2、VEGFR-3的IC50值分別為0.21、0.16、0.24nM。Tivozanib抑制腫瘤組織中的?管?成和?管通透性，并顯?出抗腫瘤活性。Tivozanib具有研究轉(zhuǎn)移性腎細胞癌(RCC)的潛?[1][2][3]。IC50&TargetVEGFR1VEGFR2VEGFR30.21nM(IC50)0.16nM(IC50)0.24nM(IC50)體外研究TivozanibinhibitsthephosphorylationofVEGFR-1,VEGFR-2andVEGFR-3[2].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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.