Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECyclosporinACat.No.:HY-B0579CASNo.:59865-13-3Synonyms:CyclosporineA;CiclosporinA;CsA分?式:C??H???N??O??分?量:1202.61作?靶點:MolecularGlues;Phosphatase;ComplementSystem;Antibiotic作?通路:PROTAC;MetabolicEnzyme/Protease;Immunology/Inflammation;Anti-infection儲存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實驗DMSO:62.5mg/mL(51.97mM;Needultrasonic)Ethanol:50mg/mL(41.58mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM0.8315mL4.1576mL8.3152mL5mM0.1663mL0.8315mL1.6630mL10mM0.0832mL0.4158mL0.8315mL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(protectfromlight)。-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)1/3MasterofBioactiveMolecules—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:2.08mg/mL(1.73mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(1.73mM);Suspendedsolution;Needultrasonic3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(1.73mM);Clearsolution4.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.62mg/mL(2.18mM);Suspendedsolution;Needultrasonic5.請依序添加每種溶劑：cornoilSolubility:50mg/mL(41.58mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性CyclosporinA(CyclosporineA)?種免疫抑制劑，能與親環(huán)素結(jié)合，抑制calcineurin活性的IC50值為7nM[3]。CyclosporinA也抑制CD11a/CD18粘附分?[8]。IC50&TargetIC50:7nM(calcineurin)體外研究CyclosporinAisabletobindwiththecyclophilininTcells[1].CyclosporinAworksbyformingaCyclophilin-CyclosporinAcomplextoinhibitcalcineurin[2].CyclosporinAinhibitscalcineurininstimulatedcellswithanIC50valueof7nM[3].CyclosporinAsuppressesthenucleartranslocationofNF-AT[4].CyclosporinAshowsaneffectonmitochondriaviapreventingtheMTPfromopeningwithanIC50of39nM[5].體內(nèi)研究CyclosporinAhasimmunosuppressiveactivity,andisactiveviaparenteralandp.o.administrationinmice,ratandguineapigs[6].CyclosporinAcanbeusedinorgantransplantationtopreventrejection[7].PROTOCOLCellAssay[3]Immunosuppressiveagentsaredissolvedinethanolatconcentrations1000-foldmorethantheconcentrationdesiredforcelltreatments.Cells(106)aresuspendedin1mLofcompletemediuminmicrocentrifugetubes;1μLofethanoloroftheethanolicsolutionofCyclosporinAisadded,andthecellsareincubatedat37°Cfor1hr.Cellsarewashedtwicewith1mLofPBSoniceandlysedin50μLofhypotonicbuffercontaining50mMTris(pH7.5);0.1mMEGTA;1mMEDTA;0.5mMdithiothreitol;and50μgofphenylmethylsulfonylfluoride,50μgofsoybeantrypsininhibitor,5μgofleupeptin,and5μgofKiker52GpermL.Lysatesaresubjectedtothreecyclesoffreezinginliquidnitrogenfollowedbythawingat30°Candthenarecentrifugedat4°Cfor10minat12,000×g.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRatsareimmunizedonday0i.p.with05mLandmicei.v.with02mLofa10%suspensionofwashedAdministration[6]sheeperythrocytes(SE).Toelicitasecondaryresponse,miceareboosted8-11weeksaftertheprimaryimmunizationwithani.v.injectionof0-2mLof025%washedSE(107cells).Forprolongedtreatmenttheanimalsreceiveontheaverage45mg/kgcyclosporinAdailyinthefoodduring13weeks.Theseratsare2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEimmunized5daysbeforekilling.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻?NatCommun.2021May18;12(1):2915.?AdvSci(Weinh).2021Jan6;8(5):2002738.?BioactMater.2023,23：300-313?ArthritisRheumatol.2022Sep3.?ProcNatlAcadSciUSA.2021Jan12;118(2):e2009539118.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HandschumacherRE,etal.Cyclophilin:aspecificcytosolicbindingproteinforcyclosporinA.Science.1984Nov2;226(4674):544-7.[2].LiuJ,etal.Calcineurinisacommontargetofcyclophilin-cyclosporinAandFKBP-FK506complexes.Cell.1991Aug23;66(4):807-15.[3].FrumanDA,etal.CalcineurinphosphataseactivityinTlymphocytesisinhibitedbyFK506andcyclosporinA.ProcNatlAcadSciUSA.1992May1;89(9):3686-90.[4].FlanaganWM,etal.NuclearassociationofaT-celltranscriptionfactorblockedbyFK-506andcyclosporinA.Nature.1991Aug29;352(6338):803-7.[5].NicolliA,etal.Interactionsofcyclophilinwiththemitochondrialinnermembraneandregulationofthepermeabilitytransitionpore,andcyclosporinA-sensitivechannel.JBiolChem.1996Jan26;271(4):2185-92.[6].BorelJF,etal.Effectsofthenewanti-lymphocyticpeptidecyclosporinAinanimals.Immunology.1977Jun;32(6):1017-25.[7].Williams,R,etal.RandomisedtrialcomparingFK506andcyclosporininpreventionofliverallograftrejection.EuropeanFK506MulticentreLiverStudyGroup.Lancet,1994,344(8920),423-428.[8].DalmarcoEM,etal.CyclosporinAinhibitsCD11a/CD18adhesionmoleculesduetoinhibitionofTNFalphaandIL-1betalevelsinthemousemodelofp