SJ988497-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESJ988497Cat.No.:HY-151902CASNo.:2595365-41-4分⼦式:C₃₆H₃₆N₁₀O₅分⼦量:688.74作⽤靶点:PROTACs;JAK作⽤通路:PROTAC;Epigenetics;JAK/STATSignaling;ProteinTyrosineKinase/RTK;StemCell/Wnt储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性SJ988497⼀种PROTACJAK2降解剂。SJ988497可有效地抑制CRLF2重排(CRLF2r)细胞的增殖并降解CRBN新底物GSPT1。SJ988497由Ruxolitinib(HY-50856)衍⽣物、连接⼦和CRBN配体Pomalidomide组成。SJ988497可⽤于急性淋巴细胞⽩⾎病(ALL)的研究。IC50&TargetJAK2体外研究SJ988497(compound7)increasescellpermeabilityintheCaco-2assay,withtheapparentpermeabilitycoefficient(Papp)of19.12nm/s[1].SJ988497inhibitsparentalMHH-CALL-4cellswithanEC50of0.4nM,inhibitsCRBN-KDMHH–CALL-4cellswithanEC50of3456.2nM,andcanbeblockedby30μMLenalidomide(HY-A0003)[1].SJ988497(1h,1μM)resultsincomparableJAKinhibitioninMHH–CALL-4cells[1].CellViabilityAssay[1]CellLine:NALM6,MHH-CALL-2,697,KOPN49,KOPN75,MHH-CALL-4cellsConcentration:0.01nM-100nMIncubationTime:72hResult:Dose-dependentlyinhibitedcellviabilityinALLcelllines.WesternBlotAnalysis[1]1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:MHH-CALL-4cellsConcentration:1nM,10nM,100nM,1μM,4μM.IncubationTime:1hResult:DegradedmultipleJAKs(JAK1>JAK3>JAK2>TYK2),andwasabolishedbyknockdownofCRBN.体内研究SJ988497(compound7)(30mg/kg,i.p.)reducesspleensizeandtumorburdens,andiswelltoleratedwithnoweightlossorperturbationinbloodcount[1].SJ988497(10-100mg/kg,i.p.,twicedaily)showedsustainedinvivoexposurewiththeplasmaconcentrationabovethecellular50%effectiveconcentrationvalueafter24hour[1].AnimalModel:NSGmiceinoculatedbyCL20SF2-Luc2aYFPcell(i.v.)[1]Dosage:30mg/kgAdministration:Intraperitonealinjection(i.p.)Result:Reducedleukemiaburdeninbonemarrow,blood,andspleen,aswellastotalbodybioluminescentimaging.REFERENCES[1].ChangY,etal.DegradationofJanuskinasesinCRLF2-rearrangedacutelymphoblasticleukemia.Blood.2021Dec9;138(23):2313-2326.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearchuseo