AZD-5991-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAZD-5991Cat.No.:HY-101533CASNo.:2143061-81-6分⼦式:C₃₅H₃₄ClN₅O₃S₂分⼦量:672.26作⽤靶点:Bcl-2Family作⽤通路:Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(37.19mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.4875mL7.4376mL14.8752mL5mM0.2975mL1.4875mL2.9750mL10mM0.1488mL0.7438mL1.4875mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.09mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.09mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.09mM);Suspendedsolution;Needultrasonic4.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.09mM);Suspendedsolution;Needultrasonic5.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.09mM);Clearsolution6.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.09mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AZD-5991⼀种有效的选择性Mcl-1抑制剂，FRET实验检测的IC50为0.7nM，SPR实验检测的Kd为0.17nM。IC50&TargetMcl-1Mcl-10.7nM(IC50)0.17nM(Kd)体外研究TheselectivityofAZD-5991isevaluatedagainstpro-survivalBcl-2familymembersusingFRETassays.AZD-5991isselectiveforMcl-1(IC500.72ꢀnM,Ki=200ꢀpM)vs.Bcl-2(IC50=20ꢀµM,Ki=6.8ꢀµM),Bcl-xL(IC50=36ꢀµM,Ki=18ꢀµM),Bcl-w(IC50=49ꢀµM,Ki=25ꢀµM),andBfl-1(IC50=24ꢀµM,Ki=12ꢀµM).MOLP-8,MV4-11,andNCI-H23cellsaretreatedwithAZD5991(EC50=0.033,0.024,0.19ꢀµM,respectively).AZD5991bindsdirectlytoMcl-1andinducesrapidapoptosisincancercells,mostnotablymyelomaandacutemyeloidleukemia,byactivatingtheBak-dependentmitochondrialapoptoticpathway.AZD5991reducesthelevelsofMcl-1proteininAZD5991-sensitivebutnotinAZD5991-resistantMMcelllinesfurthersupportingthenotionthatactivationofcaspasesbyAZD5991reducesMcl-1proteinlevelsinAZD5991-sensitivecelllines[1].体内研究Asingleintravenous(i.v.)doseofAZD5991leadstoadose-dependentantitumoreffectrangingfromtumorgrowthinhibition(TGI)totumorregression(TR).Tendaysaftertreatment,AZD5991shows52%and93%TGI(p[1].PROTOCOLAnimalMiceandRats[1]Administration[1]Inmice,drugs(e.g.,AZD5991;10-100ꢀmg/kg)aredosedintravenouslyinavolumeof5ꢀmL/kgexceptforVenetoclaxthatisdosedorallyinavolumeof10ꢀmL/kg.OnemillionMV4-11,fivemillionMOLP-8,tenmillionNCI-H929orfivemillionOCI-AML3cellsareinjectedsubcutaneouslyintherightflankofmiceinavolumeof0.1ꢀmL.Inrats,AZD5991(10-100ꢀmg/kg)isdosedintravenouslyinavolumeof10ꢀmL/kg.TenmillionMV4-11cellsareinjectedsubcutaneouslyintherightflankofratsinavolumeof0.1ꢀmL.Tumorvolumes(measuredbycaliper),animalbodyweight,andtumorconditionarerecordedtwiceweeklyforthedurationofthestudy.Thetumorvolumeiscalculated[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellDeathDis.2022Apr28;13(4):410.•CellDeathDis.2021Jul27;12(8):741.•Cells.2022Sep3;11(17):2752.•IntJCancer.2020Oct15;147(8):2176-2189.•Apoptosis.2022Aug9.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TronAE,etal.DiscoveryofMcl-1-specificinhibitorAZD5991andpreclinicalactivityinmultiplemyelomaandacutemyeloidleukemia.NatCommun.2018Dec17;9(1):5341.McePdfHeig