MS4077-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMS4077Cat.No.:HY-112156CASNo.:2230077-10-6分⼦式:C₅₅H₇₂ClN₉O₁₃S分⼦量:1134.73作⽤靶点:PROTACs;Anaplasticlymphomakinase(ALK)作⽤通路:PROTAC;ProteinTyrosineKinase/RTK储存⽅式:-20°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:110mg/mL(96.94mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM0.8813mL4.4063mL8.8127mL5mM0.1763mL0.8813mL1.7625mL10mM0.0881mL0.4406mL0.8813mL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(sealedstorage,awayfrommoistureandlight)。-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:6mg/mL(5.29mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥6mg/mL(5.29mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性MS4077Cereblon配体的间变性淋巴瘤激酶(ALK)PROTAC(降解物)，结合ALK,Kd为37nM[1]。IC50&TargetALKCereblon体外研究MS4077effectivelyinhibitscancercellproliferation.MS4077(10-3-1μM;3days)concentration-dependentlyinhibitsproliferationofSU-DHL-1ꢀcellswithanIC50ꢀofꢀ46ꢀ±ꢀ4ꢀnM.IncomparisonwithSU-DHL-1ꢀcells,theproliferationofNCI-H2228ꢀcellsislesssensitivetoMS4077(10-2-100.5μM;3days)[1].MS4077potentlyreducestheALKfusionproteinlevelsandinhibitstheALKauto-phosphorylationanddown-steamSTAT3phosphorylationinbothSU-DHL-1andNCI-H2228ꢀcellsinaconcentration-dependentmanner.InSU-DHL-1ꢀcells,MS4077reducestheNPM-ALKproteinlevelswithimpressiveDC50(50%degradation)valueofꢀ3±1ꢀnMafter16-hourtreatment.Over90%ofinhibitionofbothALKY1507andSTAT3Y705phosphorylationisachievedatthe100ꢀnMconcentration.InNCI-H2228ꢀcells,MS4077reducestheEML4-ALKproteinlevelswithsimilarDC50valueofꢀ34±9ꢀnMafter16-hourtreatment.Atthe100ꢀnMconcentration,NCI-H2228ꢀcellsreducesmorethan90%ofEML4-ALKproteinlevels[1].CellViabilityAssay[1]CellLine:SU-DHL-1andNCI-H2228cellsConcentration:10-3,10-2.5,10-2,10-1.5,10-1,10-0.5,and1μMforSU-DHL-1ꢀcells;10-2,10-1.5,10-1,10-0.5,1,100.5μMforNCI-H2228ꢀcellsIncubationTime:3daysResult:InhibitedproliferationofSU-DHL-1ꢀcells(IC50=46ꢀ±ꢀ4ꢀnM).LesssensitivetotheproliferationofNCI-H2228ꢀcellsthanSU-DHL-1ꢀcells.WesternBlotAnalysis[1]CellLine:SU-DHL-1andNCI-H2228cellsConcentration:1,3,10,30,and100μMforSU-DHL-1cells;3,10,30,60,and100μMforNCI-H2228cellsIncubationTime:16ꢀhoursResult:ReducedtheNPM-ALKproteinlevelswithimpressiveDC50ofꢀ3ꢀ±ꢀ1ꢀnMinSU-DHL-1ꢀcells.ReducedtheEML4-ALKproteinlevelswithsimilarDC50ofꢀ34ꢀ±ꢀ9ꢀnMinNCI-H2228ꢀcells.REFERENCES[1].ZhangC,etal.ProteolysisTargetingChimeras(PROTACs)ofAnaplasticLymphomaKinase(ALK).EurJMedChem.2018May10;151:304-314.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Producthasnotbeenful