Edicotinib-JNJ-40346527-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEEdicotinibCat.No.:HY-109086CASNo.:1142363-52-7Synonyms:JNJ-40346527;JNJ-527分⼦式:C₂₇H₃₅N₅O₂分⼦量:461.6作⽤靶点:c-Fms作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:16.67mg/mL(36.11mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1664mL10.8319mL21.6638mL5mM0.4333mL2.1664mL4.3328mL10mM0.2166mL1.0832mL2.1664mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥1.67mg/mL(3.62mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(3.62mM);Clearsolution3.请依序添加每种溶剂：17%Polyethyleneglycol12-hydroxystearateinsalineSolubility:10mg/mL(21.66mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Edicotinib(JNJ-40346527)⼀种有效的、选择性的、具有⾎脑通透性和⼝服活性CSF-1R抑制剂，IC50为3.2nM。Edicotinib对KIT和FLT3的抑制作⽤较⼩，IC50值分别为20nM和190nM。Edicotinib抑制⼩胶质细胞的扩张，减弱⼩胶质细胞的增殖和神经退⾏性变。Edicotinib可以⽤于阿尔茨海默病和类风湿性关节炎的研究[1][2]。IC50&TargetIC50:3.2nM(CSF-1R)[1]20nM(KIT);190nM(FLT3)[2]体外研究Edicotinib(0.1nM-1μM;24hours)Leadstoadose-dependentdecreaseofCSF1RactivationandaconcurrentreductionofERK1andERK2phosphorylation.ThedoseresponsecurveshowstheeffectofJNJ-527onCSF1RandERK1/2,andtheIC50valuesare18.6nMand22.5nMforCSF1RandERK1/2,respectively[1].WesternBlotAnalysis[1]CellLine:N13microglialcellsConcentration:0.1nM,1nM,10nM,100nM,1000nMIncubationTime:24hoursResult:PreventedCSF1RandERK1/2phosphorylationinN13microglialcells体内研究Edicotinib(oralgavage;3,10,30and100mg/kg;5days)significantlyinhibitsmicroglialproliferationinME7mice.Itdiminishesthenumberofmicroglia(totalCD45+CD11b+cells)onlyatthehighestdosetestedof100mg/kg,andJNJ-527depletesupto50%ofpatrollingbloodmonocytesateverydosetested(CD45+CD11bhighLy6Cintermediate/lowcells)withonlyatendencyforareductionintheproportionofinflammatorymonocytes(Ly6Chighcells)at100mg/kg[1].Edicotinibexhibitsagoodpharmacokinetic/pharmacodynamics(PK/PD)profile,themicroglialproliferationdatashowsanEC50of196/mland69ng/gcalculatedfromplasmaticandbraincompoundconcentration,respectively[1].Edicotinib(oralgavage;30mg/kg;33days)significantlyreducesthedensityofmicrogliainCA1ofthehippocampusofME7-prionmice(PU.1+cells)byupto30%.AndtheexpressionofIL-1βisalsoreduced,butnototherinflammatorycytokines[1].AnimalModel:C57BL/6J(Harlan)mice[1]Dosage:3,10,30and100mg/kg;5days2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration:OralgavageResult:Didnotaffectmicroglialnumberswhenadministeredunder100mg/kg.AnimalModel:C57BL/6J(Harlan)mice[1]Dosage:30mg/kg;33daysAdministration:OralgavageResult:LimitedmicroglialexpansionandattenuatedbehaviouraldeficitsinME7-prionmice.REFERENCES[1].MancusoR,etal.CSF1RinhibitorJNJ-40346527attenuatesmicroglialproliferationandneurodegenerationinP301Smice.Brain.2019Oct1;142(10):3243-3264.[2].GenoveseMC,etal.ResultsfromaPhaseIIAParallelGroupStudyofJNJ-40346527,anOralCSF-1RInhibitor,inPatientswithActiveRheumatoidArthritisdespiteDisease-modifyingAntirheumaticDrugTherapy.JRheumatol.2015Oct;42(10):1752-60.McePdfHeightCaution