S-38093-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemES38093Cat.No.:HY-104003CASNo.:862896-30-8分⼦式:C₁₇H₂₄N₂O₂分⼦量:288.38作⽤靶点:HistamineReceptor作⽤通路:GPCR/GProtein;Immunology/Inflammation;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:2mg/mL(6.94mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.4676mL17.3382mL34.6765mL5mM0.6935mL3.4676mL6.9353mL10mM---------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。BIOLOGICALACTIVITY⽣物活性S38093⼀种可透过⼤脑的，具有⼝服活性的H3receptor拮抗剂，对⼤⿏，⼩⿏和⼈的H3受体具有不同的亲和⼒，Ki值分别为8.8，1.44和1.2µM。IC50&TargetKi:8.8µM(RatH3receptor),1.44µM(MouseH3receptor),1.2µM(HumanH3receptor)[2]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体外研究Incellularmodels,S38093isabletoantagonizemiceH3receptors(KB=0.65µM)andtosuppresscAMPdecreaseinducedbyanH3agonistviahumanH3receptors(KB=0.11µM).IncellsexpressingahighH3density,S38093behavesasamoderateinverseagonistatratandhumanH3receptors(EC50=9and1.7µM,respectively)[2].体内研究S38093(0.3and3ꢀmg/kg/dp.o.,28days)significantlyincreasesproliferationofprogenitorsintheDGofhippocampusinyoungadultmice.S38093(0.3ꢀmg/kg/d)treatmentsignificantlyincreasesthenumberofDCX+cellswithtertiarydendrites.S38093(0.3,1and/or3ꢀmg/kg)significantlyincreasescellproliferation,survival,andmaturationintheDGofhippocampusinagedmicerelativetovehicle.S38093(3ꢀmg/kg/dp.o.,28days)increasescellproliferationandhasastrongeffectoncellsurvival,alsoincreasesthedendriticintersectionsinbothgenotypes(one-wayANOVAwithrepeatedmeasure,pꢀTGmiceonly.Inagedmice,chronicadministrationofS38093(1and/or3ꢀmg/kg/dayp.o.,28days)reversesthisage-dependentdecreaseinBDNF-IX,BDNF-IVandBDNF-Itranscripts.Inaddition,S38093atthreetesteddoses(0.3,1and3ꢀmg/kg/d)increasesVEGFtranscriptscomparedtovehicle-agedgroup[1].Inmice,S38093significantlyincreasesexvivoN-tele-Methylhistaminecerebrallevelsfrom3mg/kgp.o.andantagonizedR-α-Methylhistamine-induceddipsogeniafrom10mg/kgi.p[2].PROTOCOLAnimalThecontextdiscriminationtaskconsistsofan8-daycontextualfeardiscriminationparadigminwhichtheAdministration[1]micehavetolearntodistinguishbetweenafearfulshockcontextandasimilarnon-shockcontext.Onday1themiceareonlyexposedtothetrainingshockcontext,andondays2-8themiceareexposedtotheshock

andthennon-shockcontextinthatordereachday.Themicearerunthroughthecontextdiscriminationtask

startingat10amandendingat2pmandarethengavagedwithvehicleorS38093at4pmeachday.The

drugandvehiclearealwaysadministeredafterbehavioraltestingtoavoidpossibleacuteeffectsofthedrug

onbehavior.Learningismeasuredbythepercenttimethemicespentfreezingandtestingisterminated

whenpercentfreezingisconsistentlysignificantlydifferentbetweenthetwocontexts.Themicearetested

after29daysofdrugtreatment.ConditioningisconductedononesideofaMed-Associatesshuttlebox

(ENV-010MC;20.3ꢀcmꢀ×ꢀ15.9ꢀcmꢀ×ꢀ21.3ꢀcmhigh)withaclearplexiglasswall,3aluminumwallsanda

stainlesssteelgridasafloor.Mousebehaviorisrecordedbydigitalvideocamerasmountedabovethe

conditioningchamber.FreezeframeandFreezeviewsoftwarareusedforrecordingandanalyzingfreezing

behavior,respectively.IntrainingcontextA,miceareallowedtohabituateinnewcagesoutsidetheroom

andarethenbroughtintotheroominthenewcages.Thehousefanandhouselightareturnedon,the

stainlesssteelgridisexposed,theplexiglasswallisupandamildanisescentisusedasanolfactorycue.

Thedoortothesounddampeningenclosureisshutforthedurationofthetrial.180ꢀsafterthemiceare

placedinthetrainingcontext,theyaredeliveredasinglefootshockof0.75ꢀmAlasting2ꢀs.15ꢀsaftertheend

ofthefootshock,themiceareplacedbackintotheirhomecages.Non-alcoholicantisepticwipesareusedto

cleanthegridsandcatchtraysinbetweentrials.Anhourlaterthemicearebroughtintotheroominpaper

bucketsandputintosimilarcontextB.Thehousefanandhouselightareturnedoff,thedoorofthe

enclosureisleftajar,plasticplacematsheetsareputintotheshuttleboxtomakeahigh-walledcircular

enclosure,theplexiglasswallisleftdownandamildlemonscentisusedastheolfactorycue.Thestainless

steelgrid,asalientfeatureofbothcontexts,remainedexposed.Themicestayedinthechambersfor180ꢀs

withoutreceivingafootshockandareplacedbackintotheirhomecages.70%ethanolisusedtocleanthe2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEgridsandcatchtraysbetweentrials.Thediscriminationratioallowedforevaluationofdiscriminationbetweenthetwocontextsandiscomputedasfollows:Aꢀ=ꢀfreezingincontextA,Bꢀ=ꢀfreezingincontextB,andthediscriminationratioꢀ=ꢀA/(Aꢀ+ꢀB).Largervaluesindicatebetterdiscrimination.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].GuillouxJP,etal.S38093,ahistamineH3antagonist/inverseagonist,promoteshippocampalneurogenesisandimprovescontextdiscriminationtaskinagedmice.SciRep.2017Feb20;7:42946.[2].SorsA,etal.MechanisticcharacterizationofS38093,anovelinve