TL12-186-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETL12-186Cat.No.:HY-130665CASNo.:2250025-88-6分?式:C??H??ClN??O?S分?量:931.46作?靶點(diǎn):PROTACs;CDK作?通路:PROTAC;CellCycle/DNADamage儲(chǔ)存?式:4°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:200mg/mL(214.72mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.0736mL5.3679mL10.7358mL5mM0.2147mL1.0736mL2.1472mL10mM0.1074mL0.5368mL1.0736mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoistureandlight)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(5.37mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥5mg/mL(5.37mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性TL12-186?種依賴于Cereblon的多激酶PROTAC降解劑。包括CDK，BTK，F(xiàn)LT3，Aurora激酶，TEC，ULK，ITK等。TL12-186抑制CDK2/cyclinA和CDK9/cyclinT1，IC50分別為73和55nM[1]。IC50&TargetCerebloncdk2/cyclinACDK9/cyclinT173nM(IC50)55nM(IC50)體外研究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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellChemBiol.2022Aug29;S2451-9456(22)00311-7.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Hai-TsangHuang,etal.AChemoproteomicApproachtoQuerytheDegradableKinomeUsingaMulti-kinaseDegrader.CellChemBiol.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2018Jan18;25(1):88-99.e6.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical