Elimusertib-BAY-1895344-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEElimusertibCat.No.:HY-101566CASNo.:1876467-74-1Synonyms:BAY1895344分⼦式:C₂₀H₂₁N₇O分⼦量:375.43作⽤靶点:ATM/ATR作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:5.4mg/mL(14.38mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6636mL13.3181mL26.6361mL5mM0.5327mL2.6636mL5.3272mL10mM0.2664mL1.3318mL2.6636mL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。-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。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：0.5%CMC-Na/salinewater1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:4mg/mL(10.65mM);Suspendedsolution;NeedultrasonicandadjustpHto3withHCl2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:0.89mg/mL(2.37mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.09mg/mL(2.90mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Elimusertib(BAY-1895344)⼀种有效、可⼝服、选择性的ATR抑制剂，IC50值为7nM，具有抗肿瘤活性。Elimusertib可⽤于实体瘤和淋巴瘤的研究。IC50&TargetATR7nM(IC50)体外研究ElimusertibpotentlyinhibitstheproliferationofabroadspectrumofhumantumorcelllineswithamedianIC50of78nM[1].Elimusertibpotentlysuppresseshydroxyurea-inducedH2AXphosphorylation(IC50:36nM)[1].ElimusertibshowsgoodselectivityagainstmTOR(ratioofIC50values:mTOR/ATR61)[3].Elimusertibrevealshighselectivityagainstotherrelatedkinases,suchasDNA-PK(IC50:332nM),ATM(IC50:1420nM),andPI3K(IC50:3270nM)[3].Elimusertibhaspotentantiproliferativeactivityagainstvariouscancercelllinesinvitro,25forexampleintheCRCcelllinesHT-29(IC50:160nM)andLoVo(IC50:71nM),andintheB-celllymphomacelllineSU-DHL-8(IC50:9nM)[3].体内研究Elimusertibshowspotentanti-tumorefficacyinmonotherapyinavarietyofxenograftmodelsofovarianandcolorectalcancer,andcausescompletetumorremissioninmantlecelllymphomamodels[2].Elimusertib(50mg/kg;p.o.;b.i.d.;3dayson/4daysoff;for11days)exhibitsstrongantitumorefficacyintheATM-mutatedSU-DHL-8(ATMK1964E)humanGCB-DLBCLcelllinederivedxenograftmodelinmice[3].Elimusertib(20mg/kg,and10mg/kgfromday14;p.o.;daily;2dayson/5daysoff;for42days)incombinationwithCarboplatin(40mg/kg;i.p.;daily;1dayon/6daysoff)resultsinsynergisticantitumoractivityintheplatinum-resistantATMproteinlowexpressingCR5038humanCRCPDXmodelinNOD/SCIDmice[3].Elimusertibexhibitsmoderateoralbioavailability(rat87%,dog51%)followingoraladministration(ratanddog0.6-1mg/kg)[3].Elimusertibexhibitsterminaleliminationhalf-lives(mouse0.17h,rat1.3and,dog1.0h)duetoplasmaclearance(3.5,1.2,and0.79L/h/kgrespectively)followingintravenousadministration(mouse,ratanddog0.3-0.5mg/kg)[3].AnimalModel:FemaleC.B-17SCIDmice,SU-DHL-8GCB-DLBCLxenograftmodel[3]Dosage:50mg/kgAdministration:Oraladministration,b.i.d.,3dayson/4daysoff,for11days2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Inhibitedtumorarea.AnimalModel:MaleWistarrats[3]Dosage:0.3-0.5mg/kgfori.v.;0.6-1mg/kgfororal(PharmacokineticAnalysis)Administration:IntravenousinjectionandoraladministrationResult:Oralbioavailability(87%),T1/2(1.3h).AnimalModel:Femalebeagledogs[3]Dosage:0.3-0.5mg/kgfori.v.;0.6-1mg/kgfororal(PharmacokineticAnalysis)Administration:IntravenousinjectionandoraladministrationResult:Oralbioavailability(51%),T1/2(1.0h).户使⽤本产品发表的科研⽂献•CancerRes.2022Jan12;canres.1707.2021.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].UlrichT.Luecking,etal.Abstract983:Identificationofpotent,highlyselectiveandorallyavailableATRinhibitorBAY1895344withfavorablePKpropertiesandpromisingefficacyinmonotherapyandcombinationinpreclinicaltumormodels.CancerResea[2].AntjeMargretWengner,etal.Abstract836:ATRinhibitorBAY1895344showspotentanti-tumorefficacyinmonotherapyandstrongcombinationpotentialwiththetargetedalphatherapyRadium-223dichlorideinpreclinicaltumormodels.CancerResearch.July[3].UlrichLücking,etal.DamageIncorporated:DiscoveryofthePotent,HighlySelective,OrallyAvailableATRInhibitorBAY1895344withFavorablePharmacokineticPropertiesandPromisingEfficacyinMonotherapyandinCombina