UMI-77-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEUMI-77Cat.No.:HY-18628CASNo.:518303-20-3分⼦式:C₁₈H₁₄BrNO₅S₂分⼦量:468.34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:≥28mg/mL(59.79mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1352mL10.6760mL21.3520mL5mM0.4270mL2.1352mL4.2704mL10mM0.2135mL1.0676mL2.1352mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.34mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.34mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性UMI-77⼀种选择性的Mcl-1抑制剂，对Mcl-1具有⾼亲和⼒(IC50=0.31μM)。UMI-77结到Mcl-1的BH3结合沟，Ki值为490nM，⽐作⽤于Bcl-2家族其他成员的选择性⾼。IC50&TargetMcl-1Bfl-1Bcl-WBcl-20.49μM(Ki)5.33μM(Ki)8.19μM(Ki)23.83μM(Ki)Bcl-xL32.99μM(Ki)体外研究CompetitivebindingcurveofUMI-77againstMcl-1isobtainedbyFPbasedbindingassayusingfluorescentlabeledBidBH3peptidewithanIC50of1.87±0.22μM.UMI-77potentlyinhibitsthecellgrowthofBxPC-3andPanc-1celllineswithIC50valuesof3.4μMand4.4μMrespectively,andshows3to5timeslesspotencyininhibitionofthecellgrowthoftwoothertestedcelllinesMiaPaCa-2(12.5μM)andAsPC-1(16.1μM).ThecellgrowthinhibitionpotencyofUMI-77correlateswiththehighestexpressionofMcl-1andBak,andlowestexpressionofBcl-xLinthesensitivecelllines,BxPC-3andPanc-1.Capan-2cellsareshowingsimilarsensitivitytoUMI-77(IC50of5.5μM)asBxPC-3andPanc-1,althoughhaslowMcl-1levels[1].体内研究UMI-77exhibitsmoderatemetabolicstabilitywithahalf-lifeof45minutes.Themaximumtolerateddose(MTD)ofUMI-77inSCIDmiceisdetermined.Administered60mg/kgi.v.for5consecutivedaysperweekfortwoweeksdoesnotcauseanylossintheanimalweightandthereisnoobvioussignoftoxicityduringthecourseofthetreatment.Increasingthedoseto80mg/kgshowsevereanimalweightloss(>20%),therefore60mg/kgisusedasatherapeuticdosefortheinvivoefficacystudies.DailytreatmentwithUMI-77for5consecutivedaysaweekfortwoweeksresultsinstatisticallysignificanttumorgrowthinhibitionby65%and56%incomparisonwiththecontrolsinday19(p[1].PROTOCOLCellAssay[1]HumanPCcelllinesAsPC-1,BxPC-3andCapan-2areculturedinRPMI1640medium,whilePanc-1andMiaPaCaareculturedinDMEMmedium,allsupplementedwith10%fetalbovineserum.Thecellgrowthinhibitionaftertreatmentwithincreasingconcentrationsofthecompounds(e.g.,UMI-77;1,10,and100μM)isdeterminedbyWST-8assay[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]ForBxPC-3subcutaneousmodel,10×106cellsaresubcutaneouslyinjectedintotheflanksof4-5weekoldfemaleseverecombinedimmunedeficientmice(ICR-SCID).Palpabletumorsstarttoappearin3-5weeks.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemETumorsaremeasuredtwiceweekly.Topreventanypainordiscomfort,miceareeuthanizedandtheirtumorsremoveoncetheyreach~1800mgburden.Tumorsarethendissectedinto50mgpiecesandre-transplantedintonaïveICR-SCIDforserialpropagation.AnimalsaretreatedwitheithervehicleorUMI-77giveni.v.(60mg/kg)ondaythreepostBxPC-3transplantationfortwoweeks(5daysaweek).Tumorweightisrecordedthroughoutthetreatmentperiod.Attheendofthetreatmentperiod,animalsareeuthanizedandtheirtumorsharvestedforproteinisolationandwesternblotanalysisforapoptoticmarkers.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CancerCellInt.2022Oct7;22(1):304.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AbulwerdiF,etal.Anovelsmall-moleculeinhibitorofmcl-1blockspancreaticcancergrowthinvitroandinvivo.MolCancerTher.2014Ma