JNJ-7777120-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEJNJ-7777120Cat.No.:HY-13508CASNo.:459168-41-3分⼦式:C₁₄H₁₆ClN₃O分⼦量:277.75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:≥50mg/mL(180.02mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.6004mL18.0018mL36.0036mL5mM0.7201mL3.6004mL7.2007mL10mM0.3600mL1.8002mL3.6004mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(9.00mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(9.00mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(9.00mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性JNJ-7777120⼀种强效的和具有选择性的组胺H4受体拮抗剂(Ki=4.5nM)。JNJ-7777120能有效阻断组胺诱导的⼩⿏⽓管肥⼤细胞从结缔组织向上⽪细胞的迁移。JNJ-7777120还能在⼩⿏Zymosan诱导的腹膜炎模型中显著阻断中性粒细胞的浸润。JNJ-7777120具有研究抗瘙痒和抗炎的较好潜⼒。IC50&TargetH4receptor体外研究JNJ-7777120(0,10,100,1000nM;~6h)showsfunctionalantagonismofthehumanandmousehistamineH4receptorsinSK-N-MCcells[1].JNJ-7777120(10µM;10min)blockshistamine-inducedchemotaxisandcalciuminfluxinmousebonemarrow-derivedmastcells[1].JNJ7777120(30-100µM;30min)inhibitsdose-dependentlytheproductionofthymusandactivation-regulatedchemokine/CCL17andmacrophage-derivedchemokine/CCL22fromantigen-stimulatedBMMC[2].CellViabilityAssay[1]CellLine:SK-N-MCcells(expressingthehumanormousehistamineH4receptor)Concentration:0,10,100,1000nMIncubationTime:~6hResult:ExhibitedantagonisticeffectonhumanandmousehistamineH4receptors.Immunofluorescence[1]CellLine:MousemastcellsConcentration:10µMIncubationTime:10minResult:ExhibitedaverypotentantagonisticeffectontheH4receptorinprimarycells.CellViabilityAssay[1]CellLine:BMMCConcentration:30-100µM2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:30minResult:SignificantlyinhibitedtheproductionofTARC(thymusandactivation-regulatedchemokine)andMDC(macrophage-derivedchemokine).体内研究JNJ-7777120showsequipotentagainstthehuman,mouse,andratreceptorsandexhibitsatleast1000-foldselectivityoverH1,H2,orH3receptors[1].JNJ-7777120hasanoralbioavailabilityof~30%inratsand100%indogs,withahalf-lifeof~3hinbothspecies[1].JNJ-7777120(20mg/kg;s.c.;singledailyfor2days)blocksthehistamine-inducedmigrationoftrachealmastcellsfromtheconnectivetissuetowardtheepitheliuminmice[1].JNJ-7777120(10mg/kg;s.c.;single)significantlyblocksneutrophilinfiltrationinamousezymosan-inducedperitonitismodel[1].AnimalModel:BALB/cmice[1].Dosage:20mg/kgAdministration:Subcutaneousinjection;singledailyfor2daysResult:Blockedhistamineinducedanincreaseinthenumberofmastcellspertrachealsectionandasignificantmigrationofmastcellstowardsthetrachealepithelium.AnimalModel:MaleoutbredSwissalbinomice(zymosan-inducedperitonitismodel)[1].Dosage:10mg/kgAdministration:Subcutaneousinjection;singleResult:Ledtoastatisticallysignificantreductionofneutrophilinfiltration.REFERENCES[1].ThurmondRL,etal.ApotentandselectivehistamineH4receptorantagonistwithanti-inflammatoryproperties.JPharmacolExpTher.2004Apr;309(1):404-13.[2].OhsawaY,etal.TheantagonismofhistamineH1andH4receptorsameliorateschronicallergicdermatitisviaanti-pruriticandanti-inflammatoryeffectsinNC/Ngamice.Allergy.2012Aug;67(8):1014-22.McePdfH