T-3775440-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemET-3775440hydrochlorideCat.No.:HY-103085CASNo.:1422535-52-1分⼦式:C₁₈H₂₃ClN₄O分⼦量:346.85作⽤靶点:HistoneDemethylase作⽤通路:Epigenetics储存⽅式:4°C,storedundernitrogen,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen,awayfrommoisture)溶解性数据体外实验DMSO:≥30.18mg/mL(87.01mM)H2O:8.33mg/mL(24.02mM;ultrasonicandwarmingandheatto60°C)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8831mL14.4155mL28.8309mL5mM0.5766mL2.8831mL5.7662mL10mM0.2883mL1.4415mL2.8831mL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(storedundernitrogen,awayfrommoisture)。-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:≥2.5mg/mL(7.21mM);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:≥2.5mg/mL(7.21mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.21mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性T-3775440(hydrochloride)⼀种赖氨酸特异性脱甲酶1(LSD1)的不可逆性抑制剂，其IC50值为2.1nM。IC50&TargetIC50:2.1nM(LSD1)[1].体外研究T-3775440demonstratesirreversibleinhibitionofrecombinanthumanLSD1,withakinact/KIvalueof1.7×105(sec−1M−1).T-3775440ishighlyselectiveforLSD1relativetoothermonoamineoxidases(e.g.,MAO-AandMAO-B),withanIC50valueof2.1nM).T-3775440blockstheproliferationofseveralcelllinesasquicklyasday3oftreatment.Notably,thegranulocyte/macrophagemarkersCD86andCD11barecommonlyupregulatedonbothTF-1aandHEL92.1.7cellsinresponsetoT-3775440treatment,whereastheerythroidmarkersCD235aandCD71aredownregulatedbythistreatment.InCMK11-5cells,CD86mRNAexpressionisalsoclearlyupregulatedbyT-3775440inaconcentration-dependentmanner,althoughonlyamodestincreaseincellsurfaceCD86expressionisobserved.T-3775440treatmentdisruptstheLSD1-GFI1Bassociationinaconcentration-dependentmanner.T-3775440decreasesLSD1bindingbutnotGFI1BbindingandincreasesthelevelofdimethylatedH3K4atthePI16locus[1].体内研究T-3775440upregulatesCD86mRNAexpressionintumorxenograftsofHEL92.1.7cellsinadose-dependentmannerfollowingtheoraladministrationofsingledosesrangingfrom3to30mg/kg.Toinvestigatetargetengagementofthiscompoundintumors,PI16expressionlevelsistestedasadirectbiomarker.Asexpected,PI16suppressionisdramaticallyreversedbyT-3775440treatment.InaTF-1a(AEL)tumorxenograftmodel,T-3775440exhibitssignificantantitumoreffects,with15-dayT/Cvaluesof15.6%and[1].PROTOCOLCellAssay[1]ThehumanleukemiacelllinesTF-1a,HEL92.1.7,CMK11-5andM07eareused.AllcellsaregrowninRPMI1640plus10%FBSandmaintainedinahumidifiedincubatorat37°Cand5%CO2.Toassesscellproliferationandviabilityinhumanleukemiacelllines,compounds(e.gT-3775440)areaddedwithdifferentconcentrations(T-3775440:0,10,50nM)at24haftercellseeding.Aftertheincubationperiod,cellsarelysedwithCellTiter-Glo,andluminescentsignalsaredetectedusinganARVOMX1420microplatereader.Forcell-cycleanalysis,cellsarefixedovernightwith70%ethanol.FixedcellsarestainedwithpropidiumiodideandanalyzedonaFACSCaliburorFACSVerseflowcytometer[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]FemaleC.B17/Icr-scid/scidJclmiceareusedandmaintainedunderspecificpathogen-freeconditions.AMLcells(2×106cells)inMatrigelareinoculatedsubcutaneouslyintotheleftflanksof6-to7-week-oldmice(day2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE0).Micearerandomizedwhenthemeantumorvolumereachedapproximately150to350mm3.Subsequently,miceareadministratedwithvehicleorT-3775440singledosesrangingfrom3to30mg/kgoncedailyon5dayson/2daysoffschedulefor2weeks.Twiceweekly,tumorsaremeasuredwithverniercalipers,andtumorvolumesarecalculated[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CancerCell.2019Aug12;36(2):123-138.e10.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].IshikawaY,etal.ANovelLSD1InhibitorT-3775440DisruptsGFI1B-ContainingComplexLeadingtoTransdifferentiationandImpairedGrowthofAMLCells.MolCa