Ilorasertib-hydrochloride-ABT-348-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIlorasertibhydrochlorideCat.No.:HY-16018ACASNo.:1847485-91-9Synonyms:ABT-348hydrochloride分?式:C??H??ClFN?O?S分?量:525作?靶點:AuroraKinase;PDGFR;VEGFR作?通路:CellCycle/DNADamage;Epigenetics;ProteinTyrosineKinase/RTK儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:41.67mg/mL(79.37mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.9048mL9.5238mL19.0476mL5mM0.3810mL1.9048mL3.8095mL10mM0.1905mL0.9524mL1.9048mL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(sealedstorage,awayfrommoisture)。-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(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：(為保證實驗結(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)實驗的?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>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(3.96mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.96mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ilorasertib(ABT-348)hydrochloride?種有效的，具有?服活性和ATP競爭性的aurora抑制劑，對auroraA,auroraB,auroraC的IC50值分別為116,5,1nM。Ilorasertibhydrochloride也?種有效的VEGF和PDGF抑制劑。Ilorasertibhydrochloride具有?于急性髓系??病(AML)和?髓增?異常綜合征(MDS)的研究潛?[1][2]。IC50&TargetAuroraCAuroraBAuroraB(Y156H)AuroraA1nM(IC50)7nM(IC50)12nM(IC50)120nM(IC50)PDGFRαPDGFRβVEGFR1VEGFR211nM(IC50)13nM(IC50)1nM(IC50)2nM(IC50)VEGFR3FLT3CSF-1Rc-KIT43nM(IC50)1nM(IC50)3nM(IC50)20nM(IC50)體外研究Ilorasertibhydrochloride(0,3,10,30nM;24h)inducesaconcentration-dependentincreaseintheextentandnumberofH1299,H460cells[2].Ilorasertibhydrochloride(1-1000nM)showsantiproliferativeactivity[2].CellViabilityAssay[2]CellLine:H1299,H460cellsConcentration:0,3,10,30nMIncubationTime:24hResult:Inducedaconcentration-dependentincreaseintheextentandnumberofcellsexhibitingpolyploidywithEC50Sof5,10nMforH1299,H460cells,respectively.CellProliferationAssay[2]CellLine:MV-4-11,SEM,K562,HCT-15,SW620,H1299,H460cellsConcentration:1-1000nMIncubationTime:Result:ShowedantiproliferativeactivitywithIC50sof0.3,1,103,6,6,2,2nMforMV-4-11,SEM,K562,HCT-15,SW620,H1299,H460cells,respectively.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體內(nèi)研究Ilorasertibhydrochloride(6.25,12.5,25mg/kg;p.o.)showsanti-tumoractivityinMV-4-11tumor-bearingSCIDmicewithTGIof80%,86%,94%at6.25,12.5,25mg/kg,respectively[1].Ilorasertibhydrochloride(6.25,12.5,25mg/kg;p.o.)showsanti-tumoractivityinSKM-1tumor-bearingSCIDmicewithTGIof38%,59%,80%at6.25,12.5,25mg/kg,respectively[1].Ilorasertibhydrochloride(0,3.75,7.5,15mg/kg;i.p.)inhibitsthehistoneH3phosphorylationat4-8hinblood-bornetumorcells[2].Ilorasertibhydrochloride(0.2mg/kg;i.v.)showsanti-VEGFactivityinmouse[2].Ilorasertibhydrochloride(20mg/kg;p.o.;onceweeklyfor3weeks)showsanti-tumoractivityinmouse[2].AnimalModel:FemaleSCID/beigemice[2]Dosage:25mg/kgAdministration:Subcutaneousminipump;24hResult:InhibitedthehistoneH3phosphorylationandthetumordrugconcentrationassociatedwith50%inhibitionofhistoneH3phosphorylation.AnimalModel:22-26g,femaleNOD/SCIDmice(xenograftmodelofmultiplemyeloma(KMS11))[2]Dosage:20mg/kgAdministration:P.o.;onceweeklyfor3weeksResult:Inhibitedthetumorgrowthinmouse.REFERENCES[1].Yi-ChunWang,etal.Abstract858:PotentinvivoactivityoftheaurorakinaseinhibitorABT-348inhumanacutemyeloidleukemiaandmyelodysplasticsyndromexenograftmodels.CancerRes(2012)72(8_Supplement):858.[2].GlaserKB,etal.PreclinicalcharacterizationofABT-348,akinaseinhibitortargetingtheaurora,vascularendothelialgrowthfactorreceptor/platelet-derivedgrowthfactorreceptor,andSrckinasefamilies.JPharmacolExpTher.2012Dec;343(3):617-2