Apremilast-CC-10004-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEApremilastCat.No.:HY-12085CASNo.:608141-41-9Synonyms:CC-10004分⼦式:C₂₂H₂₄N₂O₇S分⼦量:460.5作⽤靶点:Phosphodiesterase(PDE);Apoptosis;TNFReceptor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:44mg/mL(95.55mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1716mL10.8578mL21.7155mL5mM0.4343mL2.1716mL4.3431mL10mM0.2172mL1.0858mL2.1716mL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：0.5%CMC-Na>>0.5%Tween-801/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:5mg/mL(10.86mM);Suspenedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.43mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.43mM);Suspendedsolution;Needultrasonic4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.43mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Apremilast(CC-10004)⼀种⼝服有效的磷酸⼆酯酶4(PDE4)抑制剂，IC50为74nM。Apremilast抑制脂多糖(LPS)释放TNF-α，IC50为104nM。IC50&TargetPDE474nM(IC50)体外研究Apremilast(CC-10004)inhibitsTNF-αreleasebylipopolysaccharide(LPS)withanIC50of104nM(pIC50=6.98±0.2),whichalmostexactlyreplicatespreviousreportedTNF-αinhibitionbyApremilastonperipheralbloodmononuclearcells(PBMCs)(IC50=110nM)andwhichissimilartothepotencyofApremilastforPDE4enzymaticinhibition(IC50=74nM).TheseresultsareclearlyconsistentwiththehypothesisthatApremilastinhibitsTNF-αbyincreasingintracellularcAMPlevels.PKA,Epac1andEpac2knockdownspreventedTNF-αinhibitionandIL-10stimulationbyApremilast[1].体内研究Apremilast(CC-10004),orallyadministered(5mg/kg),significantlyinhibitsTNF-αproductionintheairpouchby39%(61±6%ofvehicle,P[1].Apremilastisanovel,oralPDE4inhibitorthathasbeenshowntoregulateinflammatorymediators.AfteroraladministrationofApremilast,ameanmaximumplasmaconcentration(Cmax)isfoundtobe67.00±14.87ng/mL.TheplasmaconcentrationofApremilastdecreasesrapidlyandiseliminatedfromplasmawithaterminalhalf-lifeof0.92±0.46h[2]PROTOCOLCellAssay[1]Raw264.7cells(100,000)aregrownin96-wellplates.After24h,cellsarestimulatedwithvehicle(finalconcentrationof0.025%DMSO)orwithApremilastattheindicatedconcentrations.After30minutescellsarestimulatedwithLPS1μg/mLfor4h.WhenstudyingCGS21680,SCH58261,ZM241385,BAY60-6583,orGS6201,theadenosinereceptorligandsareadded15minutesbeforeApremilast.Methotrexateisadded24hand1hbeforeApremilast.SupernatesarethencollectedandTNF-αlevelsarequantifiedwiththeMouseTNF-αQuantikineELISAKit.IC50(EC50)calculationsaremadeusingnon-linearregression,sigmoidaldose-response,constrainingthetopto100%andbottomto0%,allowingvariableslope,usingGraphPadPrismv6.00[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalMice[1]Administration[1][2]MalemicearegivenweeklyintraperitonealinjectionsofeitherMTX(1mg/kg)orvehicle(PBS)for4weeks.Airpouchesaregeneratedbysubcutaneousinjectionof3mLofsterileairandreinflatedwith1.5mLofsterileair2dayslater.Vehicle(0.5%carboxymethylcelluloseand0.25%Tween80)orApremilast(5mg/kg)areorallydosed,withasyringethroughablunt-endedcurvedfeedingtube,24hand1hbeforeinflammationisinducedonday6byinjectionof1mLof2%carrageenansuspension.Fourhourslater,micearekilledbyCO2narcosis,andexudatesharvestedwith2mLPBS.LeukocytesarecountedinahemocytometerchamberandconcentrationsofcytokinesaremeasuredbyELISAorbytheLuminexplatform.Rats[2]MaleSpragueDawleyrats(180-220g)areusedtostudythepharmacokineticsofApremilast.Dietisprohibitedfor12hbeforetheexperiment,butwaterisfreelyavailable.Bloodsamples(0.3mL)arecollectedfromthetailveinintoheparinized1.5mLpolythenetubesat0.25,0.5,0.75,1,1.5,2,3,4,6,8and12hafteroraladministrationofApremilast(6.0mg/kg).Thesamplesareimmediatelycentrifugedat4,000gfor8min.Theplasmaobtained(100µL)isstoredat−20°Cuntilanalysis.PlasmaApremilastconcentrationversustimedataforeachratisanalyzedbyDAS(Drugandstatistics)software.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•IntJMolMed.2021Mar;47(3):12.•EurJPharmacol.2020Oct15;885:173508.•JDermatolSci.2019Apr;94(1):244-251.•Heinrich-Heine-UniversitätDüsseldorf.MedizinischeFakultät.2022May.•BiochemBiophysRep.December2021,101118.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Perez-AsoM,etal.Apremilast,anovelphosphodiesterase4(PDE4)inhibitor,regulatesinflammationthroughmultiplecAMPdownstreameffectors.ArthritisResTher.2015Sep15;17:249.[2].ChenLG,etal.DeterminationofApremilastinRatPlasmabyUPLC-MS-MSandItsApplicat