Tacrolimus-FK506-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETacrolimusCat.No.:HY-13756CASNo.:104987-11-3Synonyms:FK506;Fujimycin;FR900506分?式:C??H??NO??分?量:804.02作?靶點(diǎn):Phosphatase;FKBP;Bacterial;Autophagy;Antibiotic作?通路:MetabolicEnzyme/Protease;Apoptosis;Autophagy;Immunology/Inflammation;Anti-infection儲(chǔ)存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥150mg/mL(186.56mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.2438mL6.2188mL12.4375mL5mM0.2488mL1.2438mL2.4875mL10mM0.1244mL0.6219mL1.2438mL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(chǔ)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(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(protectfromlight)。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)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(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(3.11mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(3.11mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(3.11mM);Clearsolution4.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.75mg/mL(3.42mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Tacrolimus(FK506)，?環(huán)內(nèi)酯類，與FK506結(jié)合蛋?(FKBP)結(jié)合形成復(fù)合物并抑制鈣調(diào)神經(jīng)磷酸酶(calcineurinphosphatase)，從?抑制T淋巴細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)和IL-2轉(zhuǎn)錄。具有強(qiáng)免疫抑制特性。IC50&TargetMacrolide體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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].