Tacrolimus-FK506-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETacrolimusCat.No.:HY-13756CASNo.:104987-11-3Synonyms:FK506;Fujimycin;FR900506分⼦式:C₄₄H₆₉NO₁₂分⼦量:804.02作⽤靶点:Phosphatase;FKBP;Bacterial;Autophagy;Antibiotic作⽤通路:MetabolicEnzyme/Protease;Apoptosis;Autophagy;Immunology/Inflammation;Anti-infection储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性数据体外实验DMSO:≥150mg/mL(186.56mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.2438mL6.2188mL12.4375mL5mM0.2488mL1.2438mL2.4875mL10mM0.1244mL0.6219mL1.2438mL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(protectfromlight)。-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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(3.11mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(3.11mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.11mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.75mg/mL(3.42mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Tacrolimus(FK506)，⼤环内酯类，与FK506结合蛋⽩(FKBP)结合形成复合物并抑制钙调神经磷酸酶(calcineurinphosphatase)，从⽽抑制T淋巴细胞信号转导和IL-2转录。具有强免疫抑制特性。IC50&TargetMacrolide体外研究Tacrolimus(FK506)inhibitscalcium-dependentevents,suchasIL-2genetranscription,NOsynthaseactivation,celldegranulation,andapoptosis.TacrolimusalsopotentiatestheactionsofglucocorticoidsandprogesteronebybindingtoFKBPscontainedwithinthehormonereceptorcomplex,preventingdegradation.TheagentmayenhanceexpressionoftheTGFβ-1geneinafashionanalogoustothatdemonstratedforCsA.TcellproliferationinresponsetoligationoftheTcellreceptorisinhibitedbyTacrolimus[1].TreatmentwithalowconcentrationofTacrolimus(FK506,10μg/L)doesnotsignificantlyaffecttheproliferationofMH3924Acells(P=0.135).UpontreatmentwithhigherconcentrationsofTacrolimus(100-1,000μg/L),theproliferationofMH3924Acellsissignificantlyenhanced(P0.05).However,whendifferentconcentrationsofAMD3100arecombinedwith100μg/LTacrolimus,theinvitroproliferationofMH3924Acellsisincreased(P[3].体内研究ThetherapeuticeffectofTacrolimusisinvestigatedonprogressionandperpetuationofcolitisbyadministeringTacrolimustoDextransulfatesodium(DSS)-treatedmicefromDays10to16orto23.AtDays17and24,colonlengthissignificantlyshortened,andcolonweightissignificantlyhigherinDSS-treatedcontrolanimalsthaninnormalanimals.Inaddition,colonweightperunitlengthinthecontrolgroupismorethantwicethatinthenormalgroup.Whileboth7and14dtreatmentwithTacrolimussignificantlysuppressesincreasesincolonweightperunitlengthinDSS-treatedanimalscomparedwiththecontrolgroup,thistreatmentdoesnotactuallyrestorethecolonshortening.Inaddition,thisinhibitoryeffectofTacrolimusonincreasesincolonweightperunitlengthismorepronouncedwith14-dthan7-dtreatment,asshownbytheinhibitorypercentages(59%vs.28%)[4].PROTOCOLCellAssay[3]TumorcellproliferationisdeterminedbytheMTTassay.Briefly,afterMH3924Acellshavereachedthelogarithmicgrowthphase,a0.2-mLcellsuspensionat1×104cells/mLisaddedintoeachwellofa96-wellplateandculturedinDMEMfor24h.Whenadherentgrowthisestablished,differentconcentrationsof2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemETacrolimus(10,100and1,000μg/L),AMD3100(10,50and100μg/L)andTacrolimus(0and100μg/L)+AMD3100(0,10,50and100μg/L)areaddedintotheplates.Untreatedcellsculturedinmediumaloneareusedascontrols.Afterculturingfor48h,10μLMTT(5g/L)areadded,andeachwellisincubatedfor6h;next,150μL/wellDMSOareadded,followedbymeasurementsoftheabsorbanceat570mmonaspectrophotometerreader.Eachwellismeasuredthreetimes,andeachsampleisassayedintriplicate[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[4]Administration[4]Six-week-oldmaleC57BL/6Jmicearemaintainedinatemperature-andhumidity-controlledroomwitha12-hlight-darkcycle.Forthemultipledosingstudy,coliticmice(n=10)areorallyadministeredTacrolimusat30mg/kgfor7d(Days10to16)or14d(Days10to23).Control(n=10)andnormalgroups(n=5)areadministeredplacebousingthesameregimen.Tacrolimusorplaceboisadministeredat10mL/kg.MiceareeuthanizedbyCO2inhalationonthedayfollowingthefinaldosing.Forthesingledosingstudy,coliticmiceareorallyadministeredTacrolimusat30mg/kgorplacebo(n=8)onceonDay7,10,17,or24.Normalmice(n=4)areadministeredplacebousingthesameregimen.MiceareeuthanizedbyCO2inhalationeighthoursafterdosing[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JExtracellVesicles.2019Dec27;9(1):1709262.•Biomaterials.2021,120757.•NPJRegenMed.2022Sep2;7(1):43.•ProcNatlAcadSciUSA.2021Jan12;118(2):e2009539118.•NanoLett.2019Jan9;19(1):124-134.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ThomsonAW,etal.ModeofactionofTacrolimus(FK506):molecularandcellularmechanisms.TherDrugMonit.1995Dec;17(6):584-91.[2].VogelKR,etal.mTORinhibitorsrescueprematurelethalityandattenuatedysregulationofGABAergic/glutamatergictranscriptioninmurinesuccinatesemialdehydedehydrogenasedeficiency(SSADHD),adisorderofGABAmetabolism.JInheritMetabDis.2016Nov;39(6):877-886.[3].