Tariquidar-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesTariquidardihydrochlorideCat.No.:HY-110377CASNo.:1992047-62-7分?式:C??H??Cl?N?O?分?量:719.65作?靶點:P-glycoprotein作?通路:MembraneTransporter/IonChannel儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Tariquidardihydrochloride(XR9576dihydrochloride)?種有效的特異性P-glycoprotein(P-gp)抑制劑，Kd為5.1nM[1]。IC50&TargetKd:5.1nM(P-gp)[1]體外研究Tariquidar(XR9576)isapotentmodulatorofP-gpmediated[3H]-Vinblastineand[3H]-Paclitaxeltransportasitincreasesthesteady-stateaccumulationofthesecytotoxicsinCHrB30cellstolevelsobservedinnon-P-gp-expressingAuxB1cells(EC50=487±50nM).[3H]-TariquidarbindstoCHrB30membraneswiththehighestaffinity(Kd=5.1±0.9nM,n=7)andabindingcapacity(Bmax)of275±15pmol/mgmembraneprotein.Incontrasttotheparentalcellline,theaccumulationof[3H]-Vinblastineisincreasedinadose-dependentfashionbythemodulatorsTariquidar(EC50=487±50nM).TheMDRmodulatorTariquidarisabletoinhibit60-70%ofthevanadate-sensitiveATPaseactivity,withpotentIC50valueof43±9nM[1].Tariquidar(XR9576)potentiatesthecytotoxicityofseveraldrugsincludingDoxorubicin,Paclitaxel,Etoposide,andVincristine;completereversalofresistanceisachievedinthepresenceof25-80nMXR9576.TariquidarisapotentinhibitorofphotoaffinitylabelingofP-gpby[3H]Azidopineimplyingadirectinteractionwiththeprotein[2].體內(nèi)研究InmicebearingtheintrinsicallyresistantMC26colontumors,coadministrationofTariquidar(XR9576)potentiatestheantitumoractivityofDoxorubicinwithoutasignificantincreaseintoxicity;maximumpotentiationisobservedat2.5-4.0mg/kgdosedeitheri.v.orp.o.Inaddition,coadministrationofTariquidar(6-12mg/kgp.o.)fullyrestorestheantitumoractivityofPaclitaxel,Etoposide,andVincristineagainsttwohighlyresistantMDRhumantumorxenografts(2780AD,H69/LX4)innudemice.Tariquidarisfoundtoalsosignificantlypotentiatetheantitumoractivityofdoxorubicinagainsts.c.MC26tumorsinvivo[2].1/3PROTOCOLCellAssay[2]Cells(EMT6AR1.08×102/well;A27805×103/well;2780AD6×103/well)areseededinto96-wellplates.After~4h,varyingconcentrationsofTariquidarareadded,andcellsareincubatedforanadditional4days(EMT6AR1.0)or6days(2780AD)beforequantificationofcellgrowthandcalculationofIC10values(concentrationresultingin10%inhibitionofcellgrowth)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]MC26tumorslurryisimplanteds.c.inBALB/cmice(day0).Theanimalsarethenrandomized,24hlater,intogroupsof15-18andtreatedoncewithvariousregimens.Tariquidarorvehicleisadministeredeitheri.v.viaalateraltailveinorp.o.withDoxorubicin(5mg/kg)orvehiclei.v.Themodulatorisadministeredeitheri.v.at2-4mg/kg(10mL/kg)atthesametimeasDoxorubicinorp.o.at2-8mg/kg(10mL/kg)1hbeforetheCytotoxicdrug.GG918isadministeredp.o.1hbeforedoxorubicin.Alloftheanimalsareweighedtwiceweekly.Theanimalsarekilledbycervicaldislocationonday14,andthetumorsareexcisedandweighed.ThedataareanalyzedbyStudent’sttest.Rats[2]MaleCDrats(3animalspertimepoint)aredosedi.v.withpaclitaxelalone[15mininfusionat10mg/kginTween80:ethanol:5%dextrose(5:10:85%v/v/v)]orincombinationwithTariquidar(10mg/kg).Tariquidarisadministeredasabolus(i.v.)dose15minbeforeinfusionofPaclitaxel.Bloodsamplesarecollectedbycardiacpunctureusingheparinizedsyringesatvarioustimesbetween0.083and48handarecentrifugedtoprepareplasma,whichisstoredat?20°Cuntilanalysis.PaclitaxelconcentrationinplasmasamplesismeasuredbyaLC-MS/MSassay.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?Small.2020Nov;16(44):e2004172.?SciBull.2016Apr;61(7):552-560.?JCerebBloodFlowMetab.2020Oct20;271678X20965500.?JCerebBloodFlowMetab.2020Jan;40(1):150-162.?JCerebBloodFlowMetab.2016Aug;36(8):1412-23.REFERENCES[1].MartinC,etal.ThemolecularinteractionofthehighaffinityreversalagentXR9576withP-glycoprotein.BrJPharmacol,1999,128(2),403-411.[2].MistryP,etal.InvitroandinvivoreversalofP-glycoprotein-mediatedmultidrugresistancebyano