TM5441-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETM5441Cat.No.:HY-101761CASNo.:1190221-43-2分⼦式:C₂₁H₁₇ClN₂O₆分⼦量:428.82作⽤靶点:PAI-1;Apoptosis作⽤通路:MetabolicEnzyme/Protease;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥300mg/mL(699.59mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3320mL11.6599mL23.3198mL5mM0.4664mL2.3320mL4.6640mL10mM0.2332mL1.1660mL2.3320mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.83mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.83mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性TM5441⼀种⼝服⽣物可利⽤的纤溶酶原激活物抑制剂-1抑制剂(PAI-1)，抑制多个癌症细胞系的IC50值在13.9到51.1μM，并诱导⼏种⼈类癌症细胞的内在调亡。TM5441减弱Nω-硝-1-精氨酸甲酯诱导的⼼脏⾼⾎压和⾎管衰⽼[1][2]。IC50&TargetIC50:13.9~51.1μM(Tumorcelllines)[1]体外研究TM5441dose-dependentlydecreasesHT1080,HCT116,Daoy,MDA-MB-231andJurkatcellswithanIC50rangingbetween13.9and51.1μM[1].TM5441increasescaspase3/7activityforbothHT1080andHCT116cellsinadosedependantmanner.TM5441increasesapoptosisinHT1080andHCT116cells[1].TM5441inducesmitochondrialdepolarization[1].Inmouseproximaltubularepithelialcells,TM5441effectivelyinhibitsPAI-1-inducedmRNAexpressionoffibrosisandinflammationmarkersandalsoreversesPAI-1-inducedinhibitionofplasminactivity[2].体内研究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.户使⽤本产品发表的科研⽂献•EurJPharmSci.2020Feb15;143:105195.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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