Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETM5441Cat.No.:HY-101761CASNo.:1190221-43-2分?式:C??H??ClN?O?分?量:428.82作?靶點:PAI-1;Apoptosis作?通路:MetabolicEnzyme/Protease;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥300mg/mL(699.59mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3320mL11.6599mL23.3198mL5mM0.4664mL2.3320mL4.6640mL10mM0.2332mL1.1660mL2.3320mL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?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，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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:≥2.5mg/mL(5.83mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.83mM);ClearsolutionBIOLOGICALACTIVITY?物活性TM5441?種?服?物可利?的纖溶酶原激活物抑制劑-1抑制劑(PAI-1)，抑制多個癌癥細胞系的IC50值在13.9到51.1μM，并誘導(dǎo)?種?類癌癥細胞的內(nèi)在調(diào)亡。TM5441減弱Nω-硝-1-精氨酸甲酯誘導(dǎo)的?臟??壓和?管衰?[1][2]。IC50&TargetIC50:13.9~51.1μM(Tumorcelllines)[1]體外研究TM5441dose-dependentlydecreasesHT1080,HCT116,Daoy,MDA-MB-231andJurkatcellswithanIC50rangingbetween13.9and51.1μM[1].TM5441increasescaspase3/7activityforbothHT1080andHCT116cellsinadosedependantmanner.TM5441increasesapoptosisinHT1080andHCT116cells[1].TM5441inducesmitochondrialdepolarization[1].Inmouseproximaltubularepithelialcells,TM5441effectivelyinhibitsPAI-1-inducedmRNAexpressionoffibrosisandinflammationmarkersandalsoreversesPAI-1-inducedinhibitionofplasminactivity[2].體內(nèi)研究OraladministrationofTM5441(20mg/kgdaily)toHT1080andHCT116xenotransplantedmiceincreasestumorcellapoptosisandhasasignificantdisruptiveeffectonthetumorvasculaturethatisassociatedwithadecreaseintumorgrowthandanincreaseinsurvival.Theaveragepeakplasmaconcentrationis11.4μMonehourafteroraladministrationandundetectablelevels23hoursafteradministration[1].TM5441attenuatesNω-nitro-l-argininemethylester-inducedcardiachypertensionandvascularsenescence,prolongslifespaninklothonullmiceandelicitsanti-tumorigenicandanti-angiogenicactivitiesincancer[3].PROTOCOLCellAssay[1]HT1080,HCT116,Daoy,MDA-MB-231andJurkatcellsaretreatedwith0-100μMTM5441for48hoursat37°C.CellviabilityismeasuredbyMTTassay[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:TM5275at50mg/kg/dayandTM5441at10mg/kg/daywereorallyadministeredincontrolanddiabeticAdministration[2]micefor16weeks.Miceweremonitoredatleastonceaday.Attheend,bloodiscollectedformeasurementofplasmaglucoseandcreatinine,urineforproteinmeasurement,andkidneysforimmunohistochemicalanalysis[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?EurJPharmSci.2020Feb15;143:105195.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].PlacencioVR,etal.SmallMoleculeInhibitorsofPlasminogenActivatorInhibitor-1ElicitAnti-TumorigenicandAnti-AngiogenicActivity.PLoSOne.2015Jul24;10(7):e0133786.[2].JeongBY,etal.NovelPlasminogenActivatorInhibitor-1InhibitorsPreventDiabeticKidneyInjuryinaMouseModel.PLoSOne.2016Jun3;11(6):e0157012.McePdfHeightCaution:Pro