Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAZD-5991Cat.No.:HY-101533CASNo.:2143061-81-6分?式:C??H??ClN?O?S?分?量:672.26作?靶點:Bcl-2Family作?通路:Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:25mg/mL(37.19mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.4875mL7.4376mL14.8752mL5mM0.2975mL1.4875mL2.9750mL10mM0.1488mL0.7438mL1.4875mL請根據產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，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，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%salineSolubility:≥2.08mg/mL(3.09mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.09mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.09mM);Suspendedsolution;Needultrasonic4.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.09mM);Suspendedsolution;Needultrasonic5.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.09mM);Clearsolution6.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.09mM);ClearsolutionBIOLOGICALACTIVITY?物活性AZD-5991?種有效的選擇性Mcl-1抑制劑，FRET實驗檢測的IC50為0.7nM，SPR實驗檢測的Kd為0.17nM。IC50&TargetMcl-1Mcl-10.7nM(IC50)0.17nM(Kd)體外研究TheselectivityofAZD-5991isevaluatedagainstpro-survivalBcl-2familymembersusingFRETassays.AZD-5991isselectiveforMcl-1(IC500.72?nM,Ki=200?pM)vs.Bcl-2(IC50=20?μM,Ki=6.8?μM),Bcl-xL(IC50=36?μM,Ki=18?μM),Bcl-w(IC50=49?μM,Ki=25?μM),andBfl-1(IC50=24?μM,Ki=12?μM).MOLP-8,MV4-11,andNCI-H23cellsaretreatedwithAZD5991(EC50=0.033,0.024,0.19?μM,respectively).AZD5991bindsdirectlytoMcl-1andinducesrapidapoptosisincancercells,mostnotablymyelomaandacutemyeloidleukemia,byactivatingtheBak-dependentmitochondrialapoptoticpathway.AZD5991reducesthelevelsofMcl-1proteininAZD5991-sensitivebutnotinAZD5991-resistantMMcelllinesfurthersupportingthenotionthatactivationofcaspasesbyAZD5991reducesMcl-1proteinlevelsinAZD5991-sensitivecelllines[1].體內研究Asingleintravenous(i.v.)doseofAZD5991leadstoadose-dependentantitumoreffectrangingfromtumorgrowthinhibition(TGI)totumorregression(TR).Tendaysaftertreatment,AZD5991shows52%and93%TGI(p[1].PROTOCOLAnimalMiceandRats[1]Administration[1]Inmice,drugs(e.g.,AZD5991;10-100?mg/kg)aredosedintravenouslyinavolumeof5?mL/kgexceptforVenetoclaxthatisdosedorallyinavolumeof10?mL/kg.OnemillionMV4-11,fivemillionMOLP-8,tenmillionNCI-H929orfivemillionOCI-AML3cellsareinjectedsubcutaneouslyintherightflankofmiceinavolumeof0.1?mL.Inrats,AZD5991(10-100?mg/kg)isdosedintravenouslyinavolumeof10?mL/kg.TenmillionMV4-11cellsareinjectedsubcutaneouslyintherightflankofratsinavolumeof0.1?mL.Tumorvolumes(measuredbycaliper),animalbodyweight,andtumorconditionarerecordedtwiceweeklyforthedurationofthestudy.Thetumorvolumeiscalculated[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發表的科研?獻?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