MCE蚂蚁淘在线

Tacrolimus(FK506)inhibitscalcium-dependentevents,suchasIL-2genetranscription,NOsynthaseactivation,celldegranulation,andapoptosis.TacrolimusalsopotentiatestheactionsofglucocorticoidsandprogesteronebybindingtoFKBPscontainedwithinthehormonereceptorcomplex,preventingdegradation.TheagentmayenhanceexpressionoftheTGFβ-1geneinafashionanalogoustothatdemonstratedforCsA.TcellproliferationinresponsetoligationoftheTcellreceptorisinhibitedbyTacrolimus^[1].Tacrolimus(FK506)isapowerfulimmunosuppressivedrugwidelyusedtopreventorganrejectionaftertransplantation.Tacrolimusinhibitothercalcineurin-dependenttranscriptionfactorsincludingtheubiquitouslyexpressedcAMPresponseelement-bindingprotein(CREB).TacrolimusinhibitCREBtranscriptionalactivityatthecoactivatorlevel.Thedepolarization-inducedtranscriptionalactivityoftheCBPC-terminusisenhancedbyoverexpressionofcalcineurinandisinhibitedbyTacrolimusinaconcentration-dependentmannerwithIC₅₀of1nMconsistentwithIC₅₀forinhibitionofcalcineurin^[3].

InVivo

Inthepleurisyinducedbycarrageenan,Tacrolimus(1mg/kg,i.p.)andDexamethasone(0.5mg/kg,i.p.)admiNISTered0.5hbeforecausesasignificantdecreaseinleukocytes,neutrophilsandexudation(P<0.01). under="" the="" same="" conditions,="" tacrolimus="" and="" dexamethasone="" do="" not="" modify="" the="" blood"s="" white="" or="" red="" cells="" (p="">0.05).Tacrolimusshowsalonglastingantiinflammatoryeffect,inhibitingleukocytesandneutrophilsforupto24h(P<0.01), whereas="" the="" inhibition="" of="" exudation="" is="" less="" marked="" (up="" to="" 2="" h)=""><0.01). these="" drugs="" caused="" a="" marked="" reduction="" in="" mpo="" activity,="" as="" well="" as="" il-1β="" and="" tnfα="" levels=""><0.01), but="" only="" tacrolimus="" inhibits="" ada="" activity=""><0.01). tacrolimus="" significantly="" inhibits="" cell="" migration="" induces="" by="" either="" bradykinin,="" histamine="" or="" substance="" p=""><>^[4].

ClinicalTrial

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References

[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].OetjenE,etal.TheimmunosuppressivedrugscyclosporinAandtacrolimusinhibitmembranedepolarization-inducedCREBtranscriptionalactivityatthecoactivatorlevel.BrJPharmacol.2005Apr;144(7):982-93.
[4].PereiraR,etal.AntiinflammatoryeffectsofTacrolimusinamousemodelofpleurisy.TransplImmunol.2006Aug;16(2):105-11.

PreparingStockSolutions

ConcentrationVolumeMass	1mg	5mg	10mg

1mM	1.2438mL	6.2188mL	12.4375mL
5mM	0.2488mL	1.2438mL	2.4875mL
10mM	0.1244mL	0.6219mL	1.2438mL

Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.

CellAssay
^[3]

Tacrolimus(FK506)isdissolvedinDMSOandstored,andthendilutedwithappropriatemediumbeforeuse^[3].

Thepancreaticisletβ-celllineHITisgrowninRPMI1640supplementedwith10%fetalcalfserum,5%horseserum,100U/mLPenicillin,and100μg/mLStreptomycin.HITcellsaretransientlytransfectedbytheDEAE-dextranmethodwith2μgofindicatorplasmidper6-cmdishand2μgofexpressionvectorper6-cmdish,unlessstatedotherwise.Roussarcomavirus-chloramphenicolacetyltransferase(0.5μgper6-cmdish)orcytomegalovirusgreenfluorescentproteinexpressionvectors(1μgper6-cmdish)areaddedassecondreporterstocontrolfortransfectionefficiency.CotransfectionsarecarriedoutwithaconstantDNAconcentration,whichismaintainedbyaddingtheemptyvector.CellsarestimulatedwithhighKCl(finalconcentration45mM)orcAMP(forskolin10μM)6hbeforeharvest,cyclosporinAorTacrolimusareadded1hbeforestimulation.Cellextractsareprepared48haftertransfection.Thechloramphenicolacetyltransferaseassayandtheluciferaseassayareperformed.FluorescenceofthegreenfluorescentproteinismeasuredinaPackardFluoroCountwithexcitationwavelengthat485nmandemissionwavelengthat530nm^[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
^[4]

Tacrolimus(FK506)isdissolvedinsterilesaline(NaCl0.9%)(Mice)^[4].

Mice^[4]
Swissmice,weighing18-22g,arerandomlyallocatedintwelvegroups:(1)Control-treatedwithsterilesaline(NaCl,0.9%,intrapleuralroute),(2)Cg(1%,ipl.),(3)Cg(1%,ipl.)plusTacrolimus(0.5-1.5mg/kg,i.p.),(4)Cg(1%,ipl.)plusdexametahasone(0.5mg/kg,i.p.),(5)BK(10nmol,ipl.),(6)BK(10nmol,ipl.)plusTacrolimus(1.0mg/kg,i.p.),(7)Bradykinin(10nmol,ipl.)plusDexamethasone(0.5mg/kg,i.p.),(8)Histamine(1μg,ipl.),Histamine(1μg,ipl.)plusTacrolimus(1.0mg/kg,i.p.),(9)Histamine(1μg,ipl.)plusDexamethasone(0.5mg/kg,i.p.),(10)SP(20nmol,ipl.,(11),SP(20nmol,ipl.)plusTacrolimus(1.0mg/kg,i.p.),and(12)SP(20nmol,ipl.)plusDexamethasone(0.5mg/kg,i.p.).TacrolimusandDexamethasoneareadministered0.5hpriortopleurisyinduction.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

[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].OetjenE,etal.TheimmunosuppressivedrugscyclosporinAandtacrolimusinhibitmembranedepolarization-inducedCREBtranscriptionalactivityatthecoactivatorlevel.BrJPharmacol.2005Apr;144(7):982-93.
[4].PereiraR,etal.AntiinflammatoryeffectsofTacrolimusinamousemodelofpleurisy.TransplImmunol.2006Aug;16(2):105-11.

MolecularWeight

804.02

Formula

C₄₄H₆₉NO₁₂

CASNo.

104987-11-3

Storage

Powder	-20°C	3years
	4°C	2years
Insolvent	-80°C	6months
	-20°C	1month

Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥28mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:98.46%

SelectBatch: