MI-538-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMI-538Cat.No.:HY-19810CASNo.:1857417-10-7分?式:C??H??F?N?OS分?量:566.6作?靶點(diǎn):EpigeneticReaderDomain作?通路:Epigenetics儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(176.49mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7649mL8.8246mL17.6491mL5mM0.3530mL1.7649mL3.5298mL10mM0.1765mL0.8825mL1.7649mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(shí)驗(yàn)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(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%salineSolubility:≥10mg/mL(17.65mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.67mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥10mg/mL(17.65mM);ClearsolutionBIOLOGICALACTIVITY?物活性MI-538menin和MLL融合蛋?相互作?的抑制劑；IC50值為21nM。IC50&TargetIC50:21nM(meninandMLLinteraction);Kd:6.5nM(menin)[1]體外研究MI-538inhibitstheproliferationofMLLleukemiacellswithaGI50of83nM.MI-538showsnoeffect(upto6μM)ongrowthofthecontrolcelllinesHL-60andHM-2,whichdonotharborMLLtranslocations,demonstratinggoodselectivitytowardMLLfusionproteintransformedcells.MI-538bindstomeninwithlownanomolaraffinity(Kd=6.5nM).Itspotentcellularactivityoriginatesfromtheimprovedbindingaffinitytomeninandpossiblyincreasedcellmembranepermeability.TreatmentwithMI-538resultsinstrongdownregulationofexpressionofHoxa9andMeis1genes.About100nM27wassufficienttoreduceby~50%Hoxa9expressioninMLL-AF9cells,andevenmorepronouncedeffectwasseenonMeis1expression[1].體內(nèi)研究TreatmentwithMI-538resultsinapronounced,about80%,reductionintheMV4;11tumorvolume,withoutcausingsubstantialsignsoftoxicityreflectedbylessthan10%reductionofthebodyweight.MI-538demonstratesmarkedlyimprovedexposure(areaunderthecurve,AUC,values),Cmax(maximumcompoundconcentration)inthebloodplasma,andthelowestvalueofclearance.Thehalf-lifeofMI-538isabout1.6h.MI-538hasalsohighoralbioavailability(~50%)[1].PROTOCOLCellAssay[1]MOLM-13,MV4;11,HL-60humanleukemiacellsaswellasMLL-AF9andHM-2murinebonemarrowcellsaretreatedwithMI-538or0.25%DMSOfor7days.Mediaarechangedatday4withviablecellnumberrestoredtotheoriginalconcentration,andMI-538areresupplied.Anamountof100μLofcellsuspensionistransferredto96-wellplatesforeachsampleinquadruplicates.CellviabilityismeasuredusingtheMTTassay.Platesarereadforabsorbanceat570nm[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Micexenograftarerandomlygroupedwitheachgroupcontainingeightmice.VehicleorMI-538(45Administration[1]mg/kg)areadministratedoncedailyatdesignateddosesusingipinjectionsfor2weeks.Bodyweightandtumorsizesaremonitoredthreetimesaweek[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cells.2021Jan19;10(1):192.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?ActaPharmacolSin.2021Apr13.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BorkinD,etal.PropertyFocusedStructure-BasedOptimizationofSmallMoleculeInhibitorsoftheProtein-ProteinInteractionbetweenMeninandMixedLineageLeukemia(MLL).JMedChem.2016Feb11;59(3):892-913.McePdfHeightCau