PSB-0777-ammonium-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEPSB0777ammoniumCat.No.:HY-136233CASNo.:2122196-16-9分⼦式:C₁₈H₂₄N₆O₇S₂分⼦量:500.55作⽤靶点:AdenosineReceptor作⽤通路:GPCR/GProtein储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCOA.BIOLOGICALACTIVITY⽣物活性PSB0777ammonium⼀种有效的选择性腺苷A2A受体激动剂，对⼤⿏和⼈A2A受体的Ki值分别为44.4nM，360nM。PSB0777ammonium对⼤⿏和⼈的A1受体的Ki值分别≥10000nM，541nM。PSB0777ammonium显⽰出较差的⼤脑渗透性和⼝服⽣物利⽤度。PSB0777ammonium具有⽤于炎性肠病(IBS)研究的潜⼒。IC50&TargetKi:44.4nM(ratA2A),360nM(humanA2A),≥10000nM(ratA1)and541nM(humanA1)[1]体外研究PSB0777ammonium(compound7)showshighselectivityfortheA2AAR(>225-fold)versustheotherAR

subtypes(Kivaluesof>10000nMand≫10000forhumanA2BreceptorandA3receptor,respectively).PSB0777ammoniumactsasanfullagonistatA2AARwithanEC50valueof117nMinCHO-K1cells[1].PSB-0777ammoniumbindshumanβ1(Ki=4.4μM)andβ3(Ki=3.3μM)adrenergicreceptors[2].PSB0777ammonium(0.1µM,1µM,10µM)increasesconcentration-dependentlyAcetylcholine(Ach,1mM)contractionsinuntreatedandinflamedratileum/jejunumpreparationsinexvivoexperiments[1].体内研究PSB0777ammonium(0.4mg/kg/day;oralgavage;fromtheday5to10)causesamarkedreductionofinflammatorycellinfiltrationandanameliorationofcolonicmucosalarchitecture[3].PSB0777ammonium(0.03,0.3,3mg/kg;i.p.)causesdose-dependenthypothermiaandhypoactivityinC57BL/6Jmice[2].PSB0777ammoniumcannotbeabsorbedsystemicallybythedigestivemucosaonceadministeredbytheoralroute.PSB0777ammonium(0.4mg/kg/day;PO)hasverylowplasmaconcentrationsinratsat30min(below5nM),andthereisnoplasmaconcentrationsat60minafteradministration.PSB0777ammonium(0.4mg/kg/day;IP)makesplasmaconcentrationswellevidentat30min,anddecreasesafter60min,andis1/2MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEnotdetectableat120and240min[3].AnimalModel:AlbinomaleSprague-Dawleyratsof200gwithOxazolone-inducedcolitis[3]Dosage:0.4mg/kgAdministration:Oralgavage;daily;fromtheday5to10Result:CausedamarkedreductionofinflammatorycellinfiltrationandanameliorationofcolonicmucosalarchitecturealoneorincombinationwithDexamethasone(1mg/kg/day).Counteractedsignificantlytheincrementofcolonicmyeloperoxidase(MPO)levelsassociatedwithcolitis.REFERENCES[1].AliEl-Tayeb,etal.DevelopmentofPolarAdenosineA2AReceptorAgonistsforInflammatoryBowelDisease:SynergismwithA2BAntagonists.ACSMedChemLett.2011Oct10;2(12):890-5.[2].JesseLeaCarlin,etal.ActivationofadenosineA2AorA2Breceptorscauseshypothermiainmice.Neuropharmacology.2018Sep1;139:268-278.[3].LAntonioli,etal.Anti-inflammatoryeffectofanovellocallyactingA2Areceptoragonistinaratmodelofoxazolone-inducedcolitis.PurinergicSignal.2018Mar;14(1):27-36.McePdfHeightCaution:Producthasnotbeenfullyvalidated