Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemES38093Cat.No.:HY-104003CASNo.:862896-30-8分?式:C??H??N?O?分?量:288.38作?靶點:HistamineReceptor作?通路:GPCR/GProtein;Immunology/Inflammation;NeuronalSignaling儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:2mg/mL(6.94mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.4676mL17.3382mL34.6765mL5mM0.6935mL3.4676mL6.9353mL10mM---------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(fù)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。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。BIOLOGICALACTIVITY?物活性S38093?種可透過?腦的，具有?服活性的H3receptor拮抗劑，對??，??和?的H3受體具有不同的親和?，Ki值分別為8.8，1.44和1.2μM。IC50&TargetKi:8.8μM(RatH3receptor),1.44μM(MouseH3receptor),1.2μM(HumanH3receptor)[2]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體外研究Incellularmodels,S38093isabletoantagonizemiceH3receptors(KB=0.65μM)andtosuppresscAMPdecreaseinducedbyanH3agonistviahumanH3receptors(KB=0.11μM).IncellsexpressingahighH3density,S38093behavesasamoderateinverseagonistatratandhumanH3receptors(EC50=9and1.7μM,respectively)[2].體內(nèi)研究S38093(0.3and3?mg/kg/dp.o.,28days)significantlyincreasesproliferationofprogenitorsintheDGofhippocampusinyoungadultmice.S38093(0.3?mg/kg/d)treatmentsignificantlyincreasesthenumberofDCX+cellswithtertiarydendrites.S38093(0.3,1and/or3?mg/kg)significantlyincreasescellproliferation,survival,andmaturationintheDGofhippocampusinagedmicerelativetovehicle.S38093(3?mg/kg/dp.o.,28days)increasescellproliferationandhasastrongeffectoncellsurvival,alsoincreasesthedendriticintersectionsinbothgenotypes(one-wayANOVAwithrepeatedmeasure,p?TGmiceonly.Inagedmice,chronicadministrationofS38093(1and/or3?mg/kg/dayp.o.,28days)reversesthisage-dependentdecreaseinBDNF-IX,BDNF-IVandBDNF-Itranscripts.Inaddition,S38093atthreetesteddoses(0.3,1and3?mg/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;20.3?cm?×?15.9?cm?×?21.3?cmhigh)withaclearplexiglasswall,3aluminumwallsanda

stainlesssteelgridasafloor.Mousebehaviorisrecordedbydigitalvideocamerasmountedabovethe

conditioningchamber.FreezeframeandFreezeviewsoftwarareusedforrecordingandanalyzingfreezing

behavior,respectively.IntrainingcontextA,miceareallowedtohabituateinnewcagesoutsidetheroom

andarethenbroughtintotheroominthenewcages.Thehousefanandhouselightareturnedon,the

stainlesssteelgridisexposed,theplexiglasswallisupandamildanisescentisusedasanolfactorycue.

Thedoortothesounddampeningenclosureisshutforthedurationofthetrial.180?safterthemiceare

placedinthetrainingcontext,theyaredeliveredasinglefootshockof0.75?mAlasting2?s.15?saftertheend

ofthefootshock,themiceareplacedbackintotheirhomecages.Non-alcoholicantisepticwipesareusedto

cleanthegridsandcatchtraysinbetweentrials.Anhourlaterthemicearebroughtintotheroominpaper

bucketsandputintosimilarcontextB.Thehousefanandhouselightareturnedoff,thedoorofthe

enclosureisleftajar,plasticplacematsheetsareputintotheshuttleboxtomakeahigh-walledcircular

enclosure,theplexiglasswallisleftdownandamildlemonscentisusedastheolfactorycue.Thestainless

steelgrid,asalientfeatureofbothcontexts,remainedexposed.Themicestayedinthechambersfor180?s

withoutreceivingafootshockandareplacedbackintotheirhomecages.70%ethanolisusedtocleanthe2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEgridsandcatchtraysbetweentrials.Thediscriminationratioallowedforevaluationofdiscriminationbetweenthetwocontextsandiscomputedasfollows:A?=?freezingincontextA,B?=?freezingincontextB,andthediscriminationratio?=?A/(A?+?B).Largervaluesindicatebetterdiscrimination.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].GuillouxJP,etal.S38093,ahistamineH3antagonist/inverseagonist,promoteshippocampalneurogenesisandimprovescontextdiscriminationtaskinagedmice.SciRep.2017Feb20;7:42946.[2].SorsA,etal.MechanisticcharacterizationofS38093,anovelinve