Toceranib-phosphate-SU11654-phosphate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEToceranibphosphateCat.No.:HY-10330ACASNo.:874819-74-6Synonyms:SU11654phosphate;PHA291639Ephosphate分⼦式:C₂₂H₂₈FN₄O₆P分⼦量:494.45作⽤靶点:PDGFR;VEGFR;c-Kit作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:2.46mg/mL(4.98mM;Needultrasonicandwarming)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0224mL10.1122mL20.2245mL5mM---------10mM---------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(sealedstorage,awayfrommoisture)。-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。BIOLOGICALACTIVITY⽣物活性Toceranibphosphate(SU11654phosphate)⼀种具有⼝服活性的酪氨酸激酶(RTK)受体抑制剂，能有效抑制PDGFR，VEGFR，Kit，抑制PDGFRβ和Flk-1/KDR的Ki值分别为5nM和6nM。Toceranibphosphate具有抗肿瘤和抗⾎管⽣成活性，可⽤于⽝肥⼤细胞肿瘤的研究[1][2]。1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIC50&TargetPDGFRβFlk-15nM(Ki)6nM(Ki)体外研究Toceranibphosphate(PHA291639phosphate)isaselectiveinhibitorofthetyrosinekinaseactivityofseveralmembersofthesplitkinaseRTKfamily,includingPDGFRandFlk-1/KDR,withKisof5and6nM,respectively[1].ToexploremechanismsofacquiredToceranib(TOC)resistanceincanineMCT,threeresistantsublinesaregeneratedfromtheToceranib-sensitiveexon11ITDc-kitmutantC2celllinedesignatedTR1,TR2,andTR3.GrowthoftheparentalC2cellsisinhibitedbyToceranibinadose-dependentmannerwithanIC50of50>ꢀ1,000nM).SensitivitytothreeotherKITRTKinhibitorsissimilartotheobservedresistancetoToceranib.Theparentallineaswellasallthreesublinesretainssensitivitytothecytotoxicagentsvinblastine(VBL)andCCNU.Following72hrcultureinthepresenceofincreasingconcentrationsofToceranib,treatmentnaïve,parentalC2cellsdetachfromthecultureflaskandbecomerounded,shrunken,andclumpedwithincreasedexposuretoToceranib.Incontrast,Toceranib-inducedmorphologicdifferencesarenotidentifiedintheresistantsublines[2].体内研究AdministrationofToceranibphosphate(PHA291639phosphate)significantlydecreasesthenumberandpercentageofTregintheperipheralbloodofdogswithcancer.DogsreceivingToceranibphosphate(PHA291639phosphate)andcyclophosphamide(CYC)demonstrateasignificantincreaseinserumconcentrationsofIFN-γ,whichisinverselycorrelatedwithTregnumbersafter6weeksofcombinationtreatment[3].PROTOCOLCellAssay[2]Thec-kitmutantcanineC2mastocytomacellline,derivedfromaspontaneouslyoccurringcutaneousmastcelltumors(MCTs),isusedastheparentalcellline.CellsarepropagatedinRPMI1640supplementedwith2mML-glutamine,10%FBS,100g/mLStreptomycin,and100U/mLPenicillinina37°Cincubatorunderahumidifiedatmosphereof5%CO2.Toceranib-resistantC2cellsareselectedbygrowingC2cellsinconcentrationsofToceranibrangingfrom0.02uMto0.3uMandincreasingin0.025-0.05uMincrements.Threeindependent,Toceranib-resistantsublinesareestablishedoveraperiodof7months[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalDogs[3]Administration[3]Fifteenclient-owneddogswithadvancedtumorsareused.DogsreceiveToceranibat2.75mg/kgonceeveryotherday.After2weeks,oralcyclophosphamide(CYC)isaddedat15mg/m2daily.NumbersofTregandlymphocytesubsetsaremeasuredinbloodbyflowcytometryduringthe8-weekstudyperiod.SerumconcentrationsofIFN-γaremeasuredbyELISA.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].LondonCA,etal.PhaseIdose-escalatingstudyofSU11654,asmallmoleculereceptortyrosinekinaseinhibitor,indogswithspontaneousmalignancies.ClinCancerRes.2003Jul;9(7):2755-68.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[2].HalseyCH,etal.Developmentofaninvitromodelofacquiredresistancetotoceranibphosphate(Palladia?)incaninemastcelltumor.BMCVetRes.2014May6;10:105.[3].MitchellL,etal.Clinicalandimmunomodulatoryeffectsoftoceranibcombinedwithlow-dosecyclophosphamideindogswithcancer.JVetInternMed.2012Mar-Apr;26(2):355-62.[4].LondonC,MathieT,StingleN,etal.Preliminaryevidenceforbiologicactivityoftoceranibphosphate(Palladia(®))insolidtumours.VetCompOncol.