MRX-2843-UNC2371-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMRX-2843Cat.No.:HY-101549CASNo.:1429882-07-4Synonyms:UNC2371分?式:C??H??N?O分?量:488.67作?靶點:FLT3作?通路:ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:20mg/mL(40.93mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0464mL10.2319mL20.4637mL5mM0.4093mL2.0464mL4.0927mL10mM0.2046mL1.0232mL2.0464mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:2mg/mL(4.09mM);Clearsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2mg/mL(4.09mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.26mM);ClearsolutionBIOLOGICALACTIVITY?物活性MRX-2843(UNC2371)?種具有?服活性的、ATP競爭性的MERTK和FLT3酪氨酸激酶抑制劑(TKI)，IC50分別為1.3nM和0.64nM。IC50&TargetMERTK,FLT3[1]體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cells.2022Sep3;11(17):2752.?Vaccines.2021,9(11),1294.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MinsonKA,etal.TheMERTK/FLT3inhibitorMRX-2843overcomesresistance-conferringFLT3mutationsinacute