Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZibotentanCat.No.:HY-10088CASNo.:186497-07-4Synonyms:ZD4054分?式:C??H??N?O?S分?量:424.43作?靶點(diǎn):EndothelinReceptor;Apoptosis作?通路:GPCR/GProtein;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:25mg/mL(58.90mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3561mL11.7805mL23.5610mL5mM0.4712mL2.3561mL4.7122mL10mM0.2356mL1.1781mL2.3561mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?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(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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>>90%cornoil1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(5.89mM);ClearsolutionBIOLOGICALACTIVITY?物活性Zibotentan(ZD4054)?種有效的，選擇性的，具有?服活性的內(nèi)?素A(ETA)受體拮抗劑，Ki為13nM。Zibotentan對ETB沒有抑制作?。Zibotentan具有抗癌作?，可?于去勢抵抗性前列腺癌(CRPC)的研究。IC50&TargetETA13nM(Ki)體外研究Zibotentanpotentlyinhibitsthebindingof125iodine-ET-1toclonedhumanETAexpressedinmouseerythroleukaemiccells,withapIC50(concentrationtoinhibit50%ofbinding)valueof22nM[1].Zibotentan(48hours)treatmentincreasesthenumberofearlyapoptoticcellsinserum-starvedA2780WTcells[2].Zibotentan(ZD4054;1μM;24hours)treatmentshowssignificantinhibitionofcellproliferationinserum-starvedHEY,OVCA433,SKOV-3,andA-2780cells[3].Zibotentan(ZD4054;1μM;48hours)treatmentinducesanincreaseinapoptoticcells.Zibotentaninhibitsbcl-2andactivatescaspase-3andpoly(ADP-ribose)polymeraseproteins.[3].Zibotentan(ZD4054;1μM)decreasestheendogenousET-1-inducedphosphorylation/activationofbothkinases(AKTandp42/44MAPK)inHEYcells[3].ZibotentantreatmentalsoresultsinareductionofETAR-drivenangiogenesisandinvasivemediators,suchasvascularendothelialgrowthfactor,cyclooxygenase-1/2,andmatrixmetalloproteinase(MMP)[3].CellProliferationAssay[3]CellLine:HEY,OVCA433,SKOV-3,andA-2780cellsConcentration:1μMIncubationTime:24hoursResult:Showedsignificantinhibitionofcellproliferation.ApoptosisAnalysis[3]CellLine:HEYandOVCA433cellsConcentration:1μMIncubationTime:48hoursResult:Inducedanincreaseinapoptoticcells.體內(nèi)研究Zibotentan(10mg/kg;intraperitonealinjection;daily;for21days)treatmentsignificantlyinhibitstumorgrowthinmice.AndZibotentantreatmentincreasesE-cadherinexpression[2].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:Femaleathymic(nu+/nu+)mice(4-6weekofage)injectedwithwild-typeA2780cells[2]Dosage:10mg/kgAdministration:Intraperitonealinjection;daily;for21daysResult:Showedsignificantinhibitionintumorgrowthinmice.REFERENCES[1].CDMorris,etal.SpecificinhibitionoftheendothelinAreceptorwithZD4054:clinicalandpre-clinicalevidence.BrJCancer.2005Jun20;92(12):2148-52.[2].LauraRosanò,etal.AcquisitionofchemoresistanceandEMTphenotypeislinkedwithactivationoftheendothelinAreceptorpathwayinovariancarcinomacells.ClinCancerRes.2011Apr15;17(8):2350-60.[3].LauraRosanò,etal.ZD4054,aspecificantagonistoftheendothelinAreceptor,inhibitstumorgrowthandenhancespaclitaxelactivityinhumanovariancarcinomainvitroandinvivo.MolCancerTher.2007Jul;6(7):2003-11.McePdfHeightCaution:Productha