MS4077-DataSheet-生命科學(xué)試劑-MedChemExpressVIP

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMS4077Cat.No.:HY-112156CASNo.:2230077-10-6分?式:C??H??ClN?O??S分?量:1134.73作?靶點(diǎn):PROTACs;Anaplasticlymphomakinase(ALK)作?通路:PROTAC;ProteinTyrosineKinase/RTK儲存?式:-20°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:110mg/mL(96.94mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM0.8813mL4.4063mL8.8127mL5mM0.1763mL0.8813mL1.7625mL10mM0.0881mL0.4406mL0.8813mL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(sealedstorage,awayfrommoistureandlight)。-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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:6mg/mL(5.29mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥6mg/mL(5.29mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性MS4077Cereblon配體的間變性淋巴瘤激酶(ALK)PROTAC(降解物)，結(jié)合ALK,Kd為37nM[1]。IC50&TargetALKCereblon體外研究MS4077effectivelyinhibitscancercellproliferation.MS4077(10-3-1μM;3days)concentration-dependentlyinhibitsproliferationofSU-DHL-1?cellswithanIC50?of?46?±?4?nM.IncomparisonwithSU-DHL-1?cells,theproliferationofNCI-H2228?cellsislesssensitivetoMS4077(10-2-100.5μM;3days)[1].MS4077potentlyreducestheALKfusionproteinlevelsandinhibitstheALKauto-phosphorylationanddown-steamSTAT3phosphorylationinbothSU-DHL-1andNCI-H2228?cellsinaconcentration-dependentmanner.InSU-DHL-1?cells,MS4077reducestheNPM-ALKproteinlevelswithimpressiveDC50(50%degradation)valueof?3±1?nMafter16-hourtreatment.Over90%ofinhibitionofbothALKY1507andSTAT3Y705phosphorylationisachievedatthe100?nMconcentration.InNCI-H2228?cells,MS4077reducestheEML4-ALKproteinlevelswithsimilarDC50valueof?34±9?nMafter16-hourtreatment.Atthe100?nMconcentration,NCI-H2228?cellsreducesmorethan90%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-1?cells;10-2,10-1.5,10-1,10-0.5,1,100.5μMforNCI-H2228?cellsIncubationTime:3daysResult:InhibitedproliferationofSU-DHL-1?cells(IC50=46?±?4?nM).LesssensitivetotheproliferationofNCI-H2228?cellsthanSU-DHL-1?cells.WesternBlotAnalysis[1]CellLine:SU-DHL-1andNCI-H2228cellsConcentration:1,3,10,30,and100μMforSU-DHL-1cells;3,10,30,60,and100μMforNCI-H2228cellsIncubationTime:16?hoursResult:ReducedtheNPM-ALKproteinlevelswithimpressiveDC50of?3?±?1?nMinSU-DHL-1?cells.ReducedtheEML4-ALKproteinlevelswithsimilarDC50of?34?±?9?nMinNCI-H2228?cells.REFERENCES[1].ZhangC,etal.ProteolysisTargetingChimeras(PROTACs)ofAnaplasticLymphomaKinase(ALK).EurJMedChem.2018May10;151:304-314.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMcePdfHeightCaution:Producthasnotbeenful