Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEElimusertibCat.No.:HY-101566CASNo.:1876467-74-1Synonyms:BAY1895344分?式:C??H??N?O分?量:375.43作?靶點(diǎn):ATM/ATR作?通路:CellCycle/DNADamage;PI3K/Akt/mTOR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:5.4mg/mL(14.38mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.6636mL13.3181mL26.6361mL5mM0.5327mL2.6636mL5.3272mL10mM0.2664mL1.3318mL2.6636mL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，請?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(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：0.5%CMC-Na/salinewater1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:4mg/mL(10.65mM);Suspendedsolution;NeedultrasonicandadjustpHto3withHCl2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:0.89mg/mL(2.37mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:1.09mg/mL(2.90mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Elimusertib(BAY-1895344)?種有效、可?服、選擇性的ATR抑制劑，IC50值為7nM，具有抗腫瘤活性。Elimusertib可?于實(shí)體瘤和淋巴瘤的研究。IC50&TargetATR7nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師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).戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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