TL12-186-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETL12-186Cat.No.:HY-130665CASNo.:2250025-88-6分⼦式:C₄₄H₅₁ClN₁₀O₉S分⼦量:931.46作⽤靶点:PROTACs;CDK作⽤通路:PROTAC;CellCycle/DNADamage储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:200mg/mL(214.72mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.0736mL5.3679mL10.7358mL5mM0.2147mL1.0736mL2.1472mL10mM0.1074mL0.5368mL1.0736mL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:≥5mg/mL(5.37mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥5mg/mL(5.37mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性TL12-186⼀种依赖于Cereblon的多激酶PROTAC降解剂。包括CDK，BTK，FLT3，Aurora激酶，TEC，ULK，ITK等。TL12-186抑制CDK2/cyclinA和CDK9/cyclinT1，IC50分别为73和55nM[1]。IC50&TargetCerebloncdk2/cyclinACDK9/cyclinT173nM(IC50)55nM(IC50)体外研究TL12-186displays>90%inhibitionof193kinasesatascreeningconcentrationof1μM[1].TL12-186displayspotentbindingtoCRBN(IC50=12nM)usinganAlphaScreenengagementassay[1].TL12-186(1-10000nM;2days)exhibitsaCRBN-dependentpharmacologicaleffect,displaying13to15-foldmorepotentinhibitionofsurvivaloftheWTcellsthantheCRBN-/-cells[1].TL12-186(10-10000nM;4hours)inhibitsSTAT1phosphorylationwithoutcausingJAK1/2degradation[1].CellProliferationAssay[1]CellLine:WTandCRBN-/-MOLM-14cells;WTandCRBN-/-MOLT-4cellsConcentration:1,10,100,1000,10000nMIncubationTime:2daysResult:ExhibitedaCRBN-dependentpharmacologicaleffect,displaying13to15-foldmorepotentinhibitionofsurvivaloftheWTcellsthantheCRBN-/-cells.WesternBlotAnalysis[1]CellLine:MOLT-4cellsConcentration:10,100,1000,10000nMIncubationTime:4hoursResult:InhibitedIFN-γ(10ng/mL)-stimulatedSTAT1phosphorylation(Y701)withoutcausingdegradationofJAK1orJAK2.户使⽤本产品发表的科研⽂献•CellChemBiol.2022Aug29;S2451-9456(22)00311-7.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Hai-TsangHuang,etal.AChemoproteomicApproachtoQuerytheDegradableKinomeUsingaMulti-kinaseDegrader.CellChemBiol.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2018Jan18;25(1):88-99.e6.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical