RUNX1-ETO-tetramerization-IN-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERUNX1/ETOtetramerization-IN-1Cat.No.:HY-151411CASNo.:88755-39-9分⼦式:C₁₈H₁₄O₇分⼦量:342.3作⽤靶点:Others作⽤通路:Others储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性RUNX1/ETOtetramerization-IN-1RUNX1/ETO四聚化的⼩分⼦抑制剂，具有抗⽩⾎病作⽤。RUNX1/ETOtetramerization-IN-1可特异靶向RUNX1/ETO的NHR2(EC50=0.25μM)，恢复RUNX1/ETO下调的因表达。RUNX1/ETOtetramerization-IN-1抑制RUNX1/ETO依赖性SKNO-1细胞增殖，在⼩⿏模型中抑制RUNX1/ETO相关肿瘤⽣长。IC50&TargetIC50:630μM(RUNX1-NHR2tetramerization)[1]体外研究RUNX1/ETOiscomposedbytheDNA-bindingRunt-domain5,theproductoftheRUNX1gene,andbyfournervyhomologyregions(NHR1-4),theproductoftheETOgene.TheNHR2domainisresponsibleforthetetramerizationofRUNX1/ETO.RUNX1/ETOtetramerization-IN-1(compound7.44)(1μMand10μM;3,5,7d)selectivelyreducestheviabilityofRUNX1/ETO-dependenthumanleukemicSKNO-1cellsinsteadofU937cells[1].RUNX1/ETOtetramerization-IN-1(compound7.44)(25μMand50μM;5d)inhibitsthegrowthofandinducesmyeloiddifferentiationinRUNX1/ETO-expressingcells(SKNO-1,Kasumi-1,andK562)[2].RUNX1/ETOtetramerization-IN-1(100μM;7d)inducesgrowth-arrestanddifferentiationofRUNX1/ETOtr-expressingCD34+progenitorcells[2].RUNX1/ETOtetramerization-IN-1(compound7.44)hasfavorablephysicochemicalandADMEpropertieswithhighaqueoussolubility,highstabilityinbufferandplasma,andalowhepaticintrinsicclearanceinvitro,withtheaqueoussolubilityof60μg/mL[3].RUNX1/ETOtetramerization-IN-1(1μMand10μM)showsapotentialtoinhibitCYP2B6,2C9,2C19,and3A4[3].RUNX1/ETOtetramerization-IN-1(compound8)(50μM;16h)inhibitsc-JunN-terminalkinase(JNK)andaffecttheJNK-pathwayincells[4].1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellViabilityAssay[1]CellLine:RUNX1/ETO-dependenthumanleukemicSKNO-1andU937cellsConcentration:1μMand10μMIncubationTime:3,5,7daysResult:InhibitedtheSKNO-1cellgrowthspecifically.CellViabilityAssay[3]CellLine:PharmacokineticpropertiesofRUNX1/ETOtetramerization-IN-1Concentration:IncubationTime:Result:Kineticsolubility(99%PBS,1%DMSO)177µMPlasmaproteinbinding(mouseplasma,60min)98.4%Plasmastability(mouseplasma,0–240min)NodegradationHepatocytestability(mousehepatocytes)2.5µL/min/millioncellsChemicalstabilityinPBS(0–4h)Nodegradation体内研究RUNX1/ETOtetramerization-IN-1(compound7.44)(200-250μg/kg;i.p.;5timesperweek;130d)delaystumorgrowthofRUNX1/ETOcellsinmice[2].AnimalModel:NSGimmunodeficientmice(NOD.Cg-PrkdcscidIl2rgtm1WjI/SzJ)injectedwithKasumi-1cells[2]Dosage:200-250μg/KgAdministration:Intraperitonealinjection;5timesperweek,for130daysResult:Reducedthedisseminationofleukemiccells,remained75%micealiveatday130post-treatment.REFERENCES[1].MetzA,etal.FromdeterminantsofRUNX1/ETOtetramerizationtosmall-moleculeprotein-proteininteractioninhibitorstargetingacutemyeloidleukemia.JChemInfModel.2013Sep23;53(9):2197-202.[2].SchandaJ,etal.SuppressionofRUNX1/ETOoncogenicactivitybyasmallmoleculeinhibitoroftetramerization.Haematologica.2017May;102(5):e170-e174.[3].GopalswamyM,etal.Biophysicalandpharmacokineticcharacterizationofasmall-moleculeinhibitorofRUNX1/ETOtetramerizationwithanti-leukemiceffects.SciRep.2022Aug19;12(1):14158.[4].KaoudTS,etal.FrominSilicoDiscoverytointra-CellularActivity:TargetingJNK-ProteinInteractionswithSmallMolecules.ACSMedChemLett.2012Aug6;3(9):721-725.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Pr