MRX-2843-UNC2371-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMRX-2843Cat.No.:HY-101549CASNo.:1429882-07-4Synonyms:UNC2371分⼦式:C₂₉H₄₀N₆O分⼦量:488.67作⽤靶点:FLT3作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:20mg/mL(40.93mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0464mL10.2319mL20.4637mL5mM0.4093mL2.0464mL4.0927mL10mM0.2046mL1.0232mL2.0464mL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。-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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:2mg/mL(4.09mM);Clearsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2mg/mL(4.09mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.26mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MRX-2843(UNC2371)⼀种具有⼝服活性的、ATP竞争性的MERTK和FLT3酪氨酸激酶抑制剂(TKI)，IC50分别为1.3nM和0.64nM。IC50&TargetMERTK,FLT3[1]体外研究IntheKasumi-1cellline,treatmentwithMRX-2843resultsindose-dependentinhibitionofMERTKphosphorylation.Decreasedphosphorylationisevidentatconcentrationsaslowas10nM,withnear-completeabrogationofMERTKactivationat100to300nM.Similarly,treatmentofKasumi-1cellswithMRX-2843mediatesinhibitionofdownstreamsignalingthroughpathwaysimportantfortumorcellsurvivalandproliferation.MRX-2843treatmentresultsinadecreaseinrelativecellnumbers,withanIC50of143.5±14.1nM,indicatingthatMRX-2843significantlyinhibitstumorcellproliferationand/orsurvival.Similarly,thereare34.1%±5.6%and67.1%±2.7%apoptoticanddeadcellsinNOMO-1culturestreatedwith150nMor300nMMRX-2843,respectively,comparewith6.8%±0.7%invehicle-treatedcultures(P[1].体内研究MRX-2843is78%orallybioavailableatadoseof3mg/kgwithaCmaxof1.3μMandat1/2of4.4hours.InMOLM-14parentalxenografts,bothquizartinibandMRX-2843increasemediansurvivalcomparewiththatofvehicle-treatedmice(172.5daysversus40daysand121daysversus36days,respectively,P[1].PROTOCOLCellAssay[1]Celllinesarecultured(10,000cells/sample)in0.35%Nobleagarona0.5%NobleagarbaselayerandoverlaidwithcRPMIcontainingkinaseinhibitor(includingMRX-2843)orvehicle.Theoverlyingmediumisreplaced2to3timesperweek,andvehicletreatmentisassessedinduplicate.After14daysor21days(Kasumi-1cellsonly),coloniesarestainedwith1mg/mLnitrotetrazoliumbluefor4hoursandcountedusingacolonycounter.Mononuclearcellsareisolatedfromhumancordbloodandsamplesfromacutemyeloidleukemia(AML)patients.Patientsamplesareculturedintriplicateatadensityof1×106cells/mLinMethoCultH4434ClassicMethylcellulose-BasedMediumwithRecombinantCytokinesforHumanCellscontainingMRX-2843orvehicle.Coloniesarecountedafter10daysusingthecolonycounter.Cordbloodcellsareincubatedfor1hourinserum-freeIscove’smodifiedDulbecco’smedium(IMDM)supplementedwithBIT9500SerumSubstitute,low-densitylipoproteins,and2-ME,andthenculturedintriplicateatadensityof2×106cells/mLinMethocultH4434methylcellulosecontainingMRX-2843orvehicle.Coloniesaremanuallycountedinablindedmannerafter14days[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalMiceareusedinthisstudy.EstablishedleukemiacelllinesormononuclearcellsisolatedfromsamplesfromAdministration[1]patientswithacutemyeloidleukemia(AML)(1×106to2.5×106permouse)aresuspendedinPBSandinjectedintothetailveinsofmicetoestablishxenografts.Allmiceare4to6monthsofageatthetimeofinjectionandaremale,withtheexceptionoftheNOMO-1,MOLM-14:D835Y,andMOLM-14:F691LNSGxenografts,whichareestablishedinfemalemice.Myeloblastsaredetectedinperipheralblood(patient-derivedxenografts)orbonemarrow(MOLM-14xenografts)samplesafterstainingwithaFITC-conjugatedanti-humanCD45Ab.SamplesareanalyzedbyflowcytometryusingaGalliosflowcytometerandKaluzasoftware.Afterengraftment,themiceareweighedandtreatedoncedailywithMRX-2843,quizartinib,orvehicleadministeredbyoralgavageinavolumeof10mL/kg.Whenmiceappearillorlostmorethan20%oftheirbodyweight,theyareeuthanized[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Cells.2022Sep3;11(17):2752.•Vaccines.2021,9(11),1294.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MinsonKA,etal.TheMERTK/FLT3inhibitorMRX-2843overcomesresistance-conferringFLT3mutationsinacute