MI-538-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMI-538Cat.No.:HY-19810CASNo.:1857417-10-7分⼦式:C₂₇H₂₅F₃N₈OS分⼦量:566.6作⽤靶点:EpigeneticReaderDomain作⽤通路:Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(176.49mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7649mL8.8246mL17.6491mL5mM0.3530mL1.7649mL3.5298mL10mM0.1765mL0.8825mL1.7649mL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%salineSolubility:≥10mg/mL(17.65mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(3.67mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥10mg/mL(17.65mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性MI-538menin和MLL融合蛋⽩相互作⽤的抑制剂；IC50值为21nM。IC50&TargetIC50:21nM(meninandMLLinteraction);Kd:6.5nM(menin)[1]体外研究MI-538inhibitstheproliferationofMLLleukemiacellswithaGI50of83nM.MI-538showsnoeffect(upto6μM)ongrowthofthecontrolcelllinesHL-60andHM-2,whichdonotharborMLLtranslocations,demonstratinggoodselectivitytowardMLLfusionproteintransformedcells.MI-538bindstomeninwithlownanomolaraffinity(Kd=6.5nM).Itspotentcellularactivityoriginatesfromtheimprovedbindingaffinitytomeninandpossiblyincreasedcellmembranepermeability.TreatmentwithMI-538resultsinstrongdownregulationofexpressionofHoxa9andMeis1genes.About100nM27wassufficienttoreduceby~50%Hoxa9expressioninMLL-AF9cells,andevenmorepronouncedeffectwasseenonMeis1expression[1].体内研究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.户使⽤本产品发表的科研⽂献•Cells.2021Jan19;10(1):192.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•ActaPharmacolSin.2021Apr13.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BorkinD,etal.PropertyFocusedStructure-BasedOptimizationofSmallMoleculeInhibitorsoftheProtein-ProteinInteractionbetweenMeninandMixedLineageLeukemia(MLL).JMedChem.2016Feb11;59(3):892-913.McePdfHeightCau