T-3775440-hydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemET-3775440hydrochlorideCat.No.:HY-103085CASNo.:1422535-52-1分?式:C??H??ClN?O分?量:346.85作?靶點:HistoneDemethylase作?通路:Epigenetics儲存?式:4°C,storedundernitrogen,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:≥30.18mg/mL(87.01mM)H2O:8.33mg/mL(24.02mM;ultrasonicandwarmingandheatto60°C)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8831mL14.4155mL28.8309mL5mM0.5766mL2.8831mL5.7662mL10mM0.2883mL1.4415mL2.8831mL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(storedundernitrogen,awayfrommoisture)。-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%salineSolubility:≥2.5mg/mL(7.21mM);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:≥2.5mg/mL(7.21mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.21mM);ClearsolutionBIOLOGICALACTIVITY?物活性T-3775440(hydrochloride)?種賴氨酸特異性脫甲酶1(LSD1)的不可逆性抑制劑，其IC50值為2.1nM。IC50&TargetIC50:2.1nM(LSD1)[1].體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemE0).Micearerandomizedwhenthemeantumorvolumereachedapproximately150to350mm3.Subsequently,miceareadministratedwithvehicleorT-3775440singledosesrangingfrom3to30mg/kgoncedailyon5dayson/2daysoffschedulefor2weeks.Twiceweekly,tumorsaremeasuredwithverniercalipers,andtumorvolumesarecalculated[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?CancerCell.2019Aug12;36(2):123-138.e10.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].IshikawaY,etal.ANovelLSD1InhibitorT-3775440DisruptsGFI1B-ContainingComplexLeadingtoTransdifferentiationandImpairedGrowthofAMLCells.MolCa