AM251-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAM251Cat.No.:HY-15443CASNo.:183232-66-8分⼦式:C₂₂H₂₁Cl₂IN₄O分⼦量:555.24作⽤靶点:CannabinoidReceptor作⽤通路:GPCR/GProtein;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(45.03mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8010mL9.0051mL18.0102mL5mM0.3602mL1.8010mL3.6020mL10mM0.1801mL0.9005mL1.8010mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.50mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.50mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AM251选择性⼤⿇素1(CB1)受体拮抗剂，IC50为8nM。AM251也GPR55的激动剂，EC50为39nM。IC50&TargetIC50:8nM(CB1receptor)[1]体外研究AM251isaCB1receptorantagonist/inverseagonist.AM251producesanagonistresponseinHEK293cells,similartothatfoundintheyeastexpressionsystem[2].AM-251reducescholesterylestersynthesisinunstimulatedandacetylatedLDL-stimulatedRaw264.7macrophages,CB2+/+andCB2-/-peritonealmacrophages[3].体内研究TheCB1antagonistAM251(3mg/kg,i.p.)decreasescapsaicin-evokednocifensivebehavior.Thissuppressiveeffectisgenotypedependent,andtheinteractionbetweentheeffectsofgenotypeandAM251approachedsignificance.PlannedcomparisonsrevealthatAM251reducesnocifensivebehaviorsinfatty-acidamidehydrolase(FAAH)KOmice(p0.2)relativetotheirrespectivevehiclecontrols.AM251(3mg/kg,i.p.)reducesthedurationofheathypersensitivityinFAAHKO(F1,9=21.43,p0.3).AM251suppressescapsaicin-evokedheathypersensitivityinatime-dependentmannerinFAAHKO(F5,9=4.349,p0.3).Post-hocanalysisrevealsthatFAAHKOmicereceivingvehicle(i.p.)displayheightenedthermalhypersensitivityat30(p[4].One-wayANOVAshowsthatAM251(AM-251)injectedintotheratssignificantlydecreasesbothofthepercentageofentriesintheopenarmsandtimespentintheopenarms,comparetocontrols.TheTukey-Kramertestanalysisrevealsasignificantreductionforthedosesof1mg/kg(P[5].PROTOCOLKinaseAssay[3]Macrophagesareseeded(2×106/well)in12-wellcultureplates.AM-251orSR144528areaddedfrom4mMstocksolutionspreparedinDMSO,1hpriortotheadditionof7-ketocholesterol(7KC)froma2mg/mLethanolstocksolution.ControlsareadjustedtoreceiveequivalentvolumesofDMSOandethanol.After16h,caspase-3activityisdetermined.AlltreatmentsaredoneintriplicateandthedatapresentedasthemeanRFLU/mgprotein±SD[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[4]Administration[4][5]Atotalof246miceweighing17-48gareusedintheseexperiments.Followingdeterminationofbaselineresponding,micereceiveasinglei.pinjection(5mL/kg)ofAMG9810(3mg/kg,n=5pergroup),AM251(3mg/kg,n=5pergroup),orvehicle(n=6pergroup).I.p.injectionsareperformed30minpriortoi.pl.capsaicinorvehicleadministration.Pawwithdrawallatenciesareassessedbeforeand10,30,60,90and120minafterintradermalinjectionofcapsaicinorvehicle.Pawwithdrawallatenciesaremeasuredinduplicateineachpawateachtimepoint,andarereportedasthemeanofthetwoduplicatedeterminationsfromeachanimal,2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEaveragedacrosssubjects.Rats[5]MaleWistarratsweighting250-350areused.Thefollowingagentsareused:CB1receptoragonist,Win-55212(0.3,1and5mg/kg,i.p.);CB1receptorantagonist,AM251(0.3,1and5mg/kg,i.p.);endocannabinoidbreakdowninhibitor,URB-597(0.03,0.1and0.3mg/kg,i.p.)inthestudy.Physiologicalsaline(0.9%sodiumchloride)isusedasthevehicle.Alldrugsarepreparedfreshlyandadministeredintraperitoneally(i.p.)inavolumeof0.1mLper10gofbodyweightoftherats.Allsubstancesaredissolvedinphysiologicalsalineandareadministrated30minbeforeelevatedplus-mazetest.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SignalTransductTargetTher.2022Jun24;7(1):190.•PsychiatRes.2021,113917.•EBioMedicine.2020Mar;53:102696.•EBioMedicine.2020Mar;53:102696.•SciChinaLifeSci.2021May27;1-21.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BrunoA,etal.Beyondradio-displacementtechniquesforidentificationofCB1ligands:thefirstapplicationofafluorescence-quenchingassay.SciRep.2014Jan20;4:3757.[2].SharirH,etal.PharmacologicalcharacterizationofGPR55,aputativecannabinoidreceptor.PharmacolTher.2010Jun;126(3):301-13.[3].ThewkeD,etal.AM-251andSR144528areacylCoA:cholesterolacyltransferaseinhibitors.BiochemBiophysResCommun.2009Apr3;381(2):181-6.[4].CareyLM,etal.Apro-nociceptivephenotypeunmaskedinmicelackingfatty-acidamidehydrolase.MolPain.2016May13;12.pii:1744806916649192.[5].KomakiA,etal.StudytheEffectofEndocannabinoidSystemonRatBehaviorinElevatedPlus-Maze.BasicClinNeurosci.